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Liu T, Melkus G, Ramsay T, Berthiaume A, Armbrecht G, Trudel G. Effect of artificial gravity on calcaneal bone marrow adipose tissue and mineral content in female and male participants in 60 days of bed rest. Exp Physiol 2025. [PMID: 40121548 DOI: 10.1113/ep091495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/17/2025] [Indexed: 03/25/2025]
Abstract
Modulation of bone marrow adipose tissue (BMAT) with prolonged inactivity was reported in haemopoietic but not in non-haemopoietic bones. This prospective randomized controlled trial submitted 16 men and 8 women to 60 days of 6° head-down-tilt bed rest. They were assigned to control, continuous or intermittent artificial gravity (AG) interventions. The AG consisted of daily centrifugation at 2g for 30 min. The serial foot pain questionnaire, MRI and dual-energy X-ray absorptiometry of the calcaneus were performed at baseline, during bed rest and at reambulation. At baseline, all groups had comparable calcaneal BMAT (P = 0.581) and bone mineral density (BMD) (P = 0.574). After bed rest, 83% of participants reported foot pain. Calcaneal BMAT was not significantly modulated after 60 days of bed rest (control, +0.2% ± 0.8%; continuous AG, +0.5% ± 1.1%; and intermittent AG, +0.1% ± 1.5%; P = 0.368). Calcaneal BMD was reduced at reambulation days 3 and 11 after 60 days of bed rest (-0.05 ± 0.06 and -0.06 ± 0.12 g/cm2, respectively; P = 0.008 and P = 0.020). The AG interventions did not significantly alter calcaneal BMAT or BMD. Sex-based analyses demonstrated calcaneal BMD loss in men but not in women. Calcaneal BMAT and BMD were inversely correlated in women and in men (Spearman's ρ, -0.40 and -0.28, respectively; both P = 0.020). Sixty days of bed rest caused foot pain and calcaneal demineralization not rescued by AG interventions. Although inversely correlated with BMD, calcaneal BMAT was not statistically increased by 60 days of head-down-tilt bed rest, possibly owing to a ceiling effect, and no bone marrow reconversion was measured at reambulation. These results have clinical relevance when returning to activities after prolonged bed rest or returning from space.
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Affiliation(s)
- Tammy Liu
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Gerd Melkus
- Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Tim Ramsay
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Alain Berthiaume
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Gabriele Armbrecht
- Department of Radiology, Centre for Muscle and Bone Research, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Guy Trudel
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Department of Medicine, Division of Physiatry, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Liu H, Liu L, Rosen CJ. Bone Marrow Adipocytes as Novel Regulators of Metabolic Homeostasis: Clinical Consequences of Bone Marrow Adiposity. Curr Obes Rep 2025; 14:9. [PMID: 39808256 DOI: 10.1007/s13679-024-00594-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/21/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE OF REVIEW Bone marrow adipose tissue is a distinctive fat depot located within the skeleton, with the potential to influence both local and systemic metabolic processes. Although significant strides have been made in understanding bone marrow adipose tissue over the past decade, many questions remain regarding their precise lineage and functional roles. RECENT FINDINGS Recent studies have highlighted bone marrow adipose tissue's involvement in continuous cross-talk with other organs and systems, exerting both endocrine and paracrine functions that play a crucial role in metabolic homeostasis, skeletal remodeling, hematopoiesis, and the progression of bone metastases. The advancement of imaging techniques, particularly cross-sectional imaging, has profoundly expanded our understanding of the complexities beyond the traditional view of bone marrow adipose tissue as an inert depot. Notably, marrow adipocytes are anatomically and functionally distinct from brown, beige, and classic white adipocytes. Emerging evidence suggests that bone marrow adipocytes, bone marrow adipose tissue originate from the differentiation of bone marrow mesenchymal stromal cells; however, they appear to be a heterogeneous population with varying metabolic profiles, lipid compositions, secretory properties, and functional responses depending on their specific location within the bone marrow. This review provides an up-to-date synthesis of current knowledge on bone marrow adipocytes, emphasizing the relationships between bone marrow adipogenesis and factors such as aging, osteoporosis, obesity, and bone marrow tumors or metastases, thereby elucidating the mechanisms underlying musculoskeletal pathophysiology.
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Affiliation(s)
- Hanghang Liu
- State Key Laboratory of Oral Diseases & National Center for Stomatology &, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China
- Maine Medical Center Research Institute, Maine Medical Center, 81 Research Drive, Scarborough, ME, 04074, USA
| | - Linyi Liu
- Maine Medical Center Research Institute, Maine Medical Center, 81 Research Drive, Scarborough, ME, 04074, USA
| | - Clifford J Rosen
- Maine Medical Center Research Institute, Maine Medical Center, 81 Research Drive, Scarborough, ME, 04074, USA.
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Chen H, Zheng M, Li M, Zheng Y, Wang X, He Y. Taurine ameliorates radiation-induced oxidative stress in bone marrow mesenchymal stromal cells and promotes osteogenesis. Free Radic Biol Med 2024; 225:805-820. [PMID: 39486749 DOI: 10.1016/j.freeradbiomed.2024.10.308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/02/2024] [Accepted: 10/29/2024] [Indexed: 11/04/2024]
Abstract
Osteoradionecrosis of the jaw (ORNJ) is a severe complication following head and neck radiotherapy that significantly impacts the quality of life of patients. Currently, there is a lack of comprehensive understanding of the microenvironmental factors involved in ORNJ. In this study, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells using scRNA-Seq and demonstrate a decrease in taurine levels in irradiated bone marrow mesenchymal stromal cells (BMSCs) through metabolomics. Compared with unirradiated BMSCs, taurine uptake in irradiated BMSCs increases. Taurine concentrations in the peripheral blood and jaws of irradiated mice are significantly lower than those in unirradiated mice (P = 0.0064 and 0.0249 respectively). Supplementation with taurine promotes osteogenic differentiation, reduces oxidative stress, and decreases DNA damage in irradiated BMSCs. Oral administration of taurine significantly improves the survival rate of irradiated mice and enhances osteogenesis in irradiated jaws. Our study highlights the role of taurine in the recovery from radiation-induced jaw injury, and suggests its potential as a non-invasive therapeutic option for combating ORNJ.
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Affiliation(s)
- Heng Chen
- Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, PR China
| | - Mengting Zheng
- Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, PR China
| | - Mengyu Li
- Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, PR China
| | - Yang Zheng
- Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, PR China
| | - Xu Wang
- Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, PR China.
| | - Yue He
- Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, PR China.
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Nelson TA, Tommasini S, Fretz JA. Deletion of the transcription factor EBF1 in perivascular stroma disrupts skeletal homeostasis and precipitates premature aging of the marrow microenvironment. Bone 2024; 187:117198. [PMID: 39002837 PMCID: PMC11410106 DOI: 10.1016/j.bone.2024.117198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 06/26/2024] [Accepted: 07/07/2024] [Indexed: 07/15/2024]
Abstract
Early B cell factor 1 (EBF1) is a transcription factor expressed by multiple lineages of stromal cells within the bone marrow. While cultures of Ebf1-deficient cells have been demonstrated to have impaired differentiation into either the osteoblast or adipogenic lineage in vitro by several groups, in vivo there has been a nominal consequence of the loss of EBF1 on skeletal development. In this study we used Prx-cre driven deletion of Ebf1 to eliminate EBF1 from the entire mesenchymal lineage of the skeleton and resolve this discrepancy. We report here that EBF1 is expressed primarily in the Mesenchymal Stem and Progenitor Cell (MSPC)-Adipo, MSPC-Osteo, and the Early Mesenchymal Progenitors, and that loss of EBF1 has a plethora of consequences to maintenance of the skeleton throughout adulthood. Stroma from the Prx-cre;Ebf1fl/fl bones had impaired osteogenic differentiation, an age-dependent loss of CFU-F, and elevated senescence accompanying Ebf1-deletion. New bone formation was reduced after 3 months, and resulted in a quiescent bone environment with fewer osteoblasts and an accompanied reduction in osteoclast-mediated remodeling. Consequently, bones were less ductile at a younger age, and deletion of EBF1 dramatically impaired fracture repair. Disruption of EBF1 in perivascular populations also rearranged the vascular network within these bones and disrupted cytokine signaling from key hematopoietic niches resulting in anemia, reductions in B cells, and myeloid skewing of marrow hematopoietic lineages. Mechanistically we observed disrupted BMP signaling within Ebf1-deficient progenitors with reduced SMAD1-phosphorylation, and elevated secretion of the soluble BMP-inhibitor Gremlin from the MSPC-Adipo cells. Ebf1-deficient progenitors also exhibited posttranslational suppression of glucocorticoid receptor expression. Together, these results suggest that EBF1 signaling is required for mesenchymal progenitor mobilization to maintain the adult skeleton, and that the primary action of EBF1 in the early mesenchymal lineage is to promote proliferation, and differentiation of these perivascular cells to sustain a healthy tissue.
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Affiliation(s)
- Tracy A Nelson
- Yale School of Medicine, Department of Orthopaedics and Rehabilitation, New Haven, CT 06510, United States of America
| | - Stephen Tommasini
- Yale School of Medicine, Department of Orthopaedics and Rehabilitation, New Haven, CT 06510, United States of America
| | - Jackie A Fretz
- Yale School of Medicine, Department of Orthopaedics and Rehabilitation, New Haven, CT 06510, United States of America.
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Garmo LC, Herroon MK, Mecca S, Wilson A, Allen DR, Agarwal M, Kim S, Petriello MC, Podgorski I. The long-chain polyfluorinated alkyl substance perfluorohexane sulfonate (PFHxS) promotes bone marrow adipogenesis. Toxicol Appl Pharmacol 2024; 491:117047. [PMID: 39111555 DOI: 10.1016/j.taap.2024.117047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/30/2024] [Accepted: 07/31/2024] [Indexed: 08/11/2024]
Abstract
Per- and polyfluoroalkyl substances (PFAS) bioaccumulate in different organ systems, including bone. While existing research highlights the adverse impact of PFAS on bone density, a critical gap remains in understanding the specific effects on the bone marrow microenvironment, especially the bone marrow adipose tissue (BMAT). Changes in BMAT have been linked to various health consequences, such as the development of osteoporosis and the progression of metastatic tumors in bone. Studies presented herein demonstrate that exposure to a mixture of five environmentally relevant PFAS compounds promotes marrow adipogenesis in vitro and in vivo. We show that among the components of the mixture, PFHxS, an alternative to PFOS, has the highest propensity to accumulate in bone and effectively promote marrow adipogenesis. Utilizing RNAseq approaches, we identified the peroxisome proliferator-activated receptor (PPAR) signaling as a top pathway modulated by PFHxS exposure. Furthermore, we provide results suggesting the activation and involvement of PPAR-gamma (PPARγ) in PFHxS-mediated bone marrow adipogenesis, especially in combination with high-fat diet. In conclusion, our findings demonstrate the potential impact of elevated PFHxS levels, particularly in occupational settings, on bone health, and specifically bone marrow adiposity. This study contributes new insights into the health risks of PFHxS exposure, urging further research on the relationship between environmental factors, diet, and adipose tissue dynamics.
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Affiliation(s)
- Laimar C Garmo
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America
| | - Mackenzie K Herroon
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America
| | - Shane Mecca
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America
| | - Alexis Wilson
- Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI, United States of America
| | - David R Allen
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America
| | - Manisha Agarwal
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America
| | - Seongho Kim
- Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI, United States of America
| | - Michael C Petriello
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, United States of America
| | - Izabela Podgorski
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States of America; Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI, United States of America.
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Schill RL, Visser J, Ashby ML, Li Z, Lewis KT, Morales-Hernandez A, Hoose KS, Maung JN, Uranga RM, Hariri H, Hermsmeyer IDK, Mori H, MacDougald OA. Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction. Front Endocrinol (Lausanne) 2024; 15:1397081. [PMID: 38887268 PMCID: PMC11180776 DOI: 10.3389/fendo.2024.1397081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 05/14/2024] [Indexed: 06/20/2024] Open
Abstract
Introduction Unlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids. Methods In this study, we utilized a recently described mouse model (BMAd-Cre) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. Nr3c1) whilst maintaining GR expression in other adipose depots. Results Mice lacking GR in BMAds (BMAd-Nr3c1 -/-) and control mice (BMAd-Nr3c1 +/+) were fed ad libitum or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female BMAd-Nr3c1-/- mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and BMAd-Nr3c1-/- mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and μCT revealed no difference in BMAT accumulation between control or BMAd-Nr3c1 -/- mice. Differences in BMAd size were not observed between BMAd-Nr3c1-/- and control mice. Interestingly, BMAd-Nr3c1-/- mice had decreased circulating white blood cell counts 4 h into the light cycle. Discussion In conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR.
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Affiliation(s)
- Rebecca L. Schill
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Jack Visser
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Mariah L. Ashby
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Ziru Li
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Kenneth T. Lewis
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Antonio Morales-Hernandez
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States
| | - Keegan S. Hoose
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Jessica N. Maung
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Romina M. Uranga
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Hadla Hariri
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Isabel D. K. Hermsmeyer
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Hiroyuki Mori
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
| | - Ormond A. MacDougald
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, United States
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
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Immune microenvironment: novel perspectives on bone regeneration disorder in osteoradionecrosis of the jaws. Cell Tissue Res 2023; 392:413-430. [PMID: 36737519 DOI: 10.1007/s00441-023-03743-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 01/18/2023] [Indexed: 02/05/2023]
Abstract
Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components.
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Vauclard A, Bellio M, Valet C, Borret M, Payrastre B, Severin S. Obesity: Effects on bone marrow homeostasis and platelet activation. Thromb Res 2022. [DOI: 10.1016/j.thromres.2022.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Chang FX, Fan DH, Huang G, He JH. Lumbar Spine Bone Mineral Density Measurement: Comparison of Dual-Energy X-Ray Absorptiometry and Fat Content Evaluation by Dixon Chemical Shift MRI. Int J Gen Med 2022; 15:6415-6424. [PMID: 35957757 PMCID: PMC9359785 DOI: 10.2147/ijgm.s370814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 07/22/2022] [Indexed: 11/23/2022] Open
Abstract
Background To assess whether the fat signal intensity and fat fraction (FF) of the lumbar vertebrae as measured on the Dixon chemical shift magnetic resonance imaging (MRI) technique can be correlated with the lumbar vertebra bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA). Methods Forty-five patients were retrospectively collected, and 180 lumbar vertebral bodies (L1-L4) were included. All patients underwent DXA and MRI examinations of the lumbar spine. Taking the T value of DXA as the gold standard and using the diagnostic criteria of the World Health Organization: T score ≥ −1.0SD as normal, −1.0 ~ −2.5SD as osteopenia, and ≤ −2.5SD as osteoporosis. Meanwhile, the signal intensity on T2WI was measured, and FF of L1-L4 vertebral bodies was calculated on MRI images. Bone marrow fat FF calculation formula: FF = [Mfat/(Mfat + Mwater)] × 100% (Mwater and Mfat refer to the total pixel signal intensity value of the region of interest in water image and lipid image, respectively). Finally, the association of signal intensity and FF with DXA was evaluated. Results Totally 180 vertebral bodies in 45 patients were enrolled. According to the T value, they were divided into the normal group (n = 70), osteopenia group (n = 40), and osteoporosis group (n = 70). The fat signal intensity of the normal group, osteopenia group, and osteoporosis group were 96.6 ± 21.8, 154.5 ± 48.7, 216.3 ± 92.6, and the FF were 30.1 ± 6.2%, 52.6 ± 7.6%, 77.5 ± 7.9%, respectively. Among the three groups, the lumbar T2 fat signal intensity and FF had statistical differences (P < 0.01). Besides, the lumbar fat signal intensity and FF were negatively related to DXA (r =−0.65 and −0.93, P < 0.01). Conclusion The fat content calculated using the Dixon chemical shift MRI had an inverse relation with BMD. Moreover, the Dixon chemical shift MRI might provide complementary information to osteoporosis-related research fields.
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Affiliation(s)
- Fei-Xia Chang
- Radiology Department, Dunhuang City Hospital, Dunhuang, 736200, People's Republic of China
| | - Dun-Hui Fan
- Department of General Surgery, Dunhuang City Hospital, Dunhuang, 736200, People's Republic of China
| | - Gang Huang
- Radiology Department, Gansu Provincial People's Hospital, Lanzhou, 730000, People's Republic of China
| | - Jian-Hong He
- Department of General Surgery, Dunhuang City Hospital, Dunhuang, 736200, People's Republic of China
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Labusca L. Adipose tissue in bone regeneration - stem cell source and beyond. World J Stem Cells 2022; 14:372-392. [PMID: 35949397 PMCID: PMC9244952 DOI: 10.4252/wjsc.v14.i6.372] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/30/2021] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
Adipose tissue (AT) is recognized as a complex organ involved in major home-ostatic body functions, such as food intake, energy balance, immunomodulation, development and growth, and functioning of the reproductive organs. The role of AT in tissue and organ homeostasis, repair and regeneration is increasingly recognized. Different AT compartments (white AT, brown AT and bone marrow AT) and their interrelation with bone metabolism will be presented. AT-derived stem cell populations - adipose-derived mesenchymal stem cells and pluripotent-like stem cells. Multilineage differentiating stress-enduring and dedifferentiated fat cells can be obtained in relatively high quantities compared to other sources. Their role in different strategies of bone and fracture healing tissue engineering and cell therapy will be described. The current use of AT- or AT-derived stem cell populations for fracture healing and bone regenerative strategies will be presented, as well as major challenges in furthering bone regenerative strategies to clinical settings.
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Affiliation(s)
- Luminita Labusca
- Magnetic Materials and Sensors, National Institute of Research and Development for Technical Physics, Iasi 700050, Romania
- Orthopedics and Traumatology, County Emergency Hospital Saint Spiridon Iasi, Iasi 700050, Romania.
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Zhang Z, Yang W, Zhu T, Wang L, Zhao X, Zhao G, Qu L, Jia Y. Genetic Parameter Estimation and Whole Sequencing Analysis of the Genetic Architecture of Chicken Keel Bending. Front Genet 2022; 13:833132. [PMID: 35401685 PMCID: PMC8984200 DOI: 10.3389/fgene.2022.833132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 02/24/2022] [Indexed: 11/18/2022] Open
Abstract
Bone health is particularly important for high-yielding commercial layer chickens. The keel of poultry is an extension of the abdomen side of the sternum along the sagittal plane and is one of the most important bones. In this study, the keel phenotype of White Leghorns laying hen flocks showed significant individual differences. To clarify its genetic mechanism, we first estimated the heritability of keel bend (KB) in White Leghorn, recorded the production performance of the chicken flock, examined the blood biochemical indexes and bone quality in KB and keel normal (KN) chickens, and performed whole-genome pooled sequencing in KB and KN chickens. We then performed selection elimination analysis to determine the genomic regions that may affect the keel phenotypes. The results show that KB is a medium heritability trait. We found that cage height had a significant effect on the KB (p < 0.01). At 48 weeks, there were significant differences in the number of eggs, the number of normal eggs, and eggshell strength (p < 0.05). The content of parathyroid hormone was lower (p < 0.01) and that of calcitonin was higher (p < 0.01) in KB chickens than in KN chickens. The differences in bone mineral density, bone strength, and bone cortical thickness of the humerus and femur were extremely significant (p < 0.01), with all being lower in KB chickens than in KN chickens. In addition, the bones of KB chickens contained more fat organization. A total of 128 genes were identified in selective sweep regions. We identified 10 important candidate genes: ACP5, WNT1, NFIX, CNN1, CALR, FKBP11, TRAPPC5, MAP2K7, RELA, and ENSGALG00000047166. Among the significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways found, we identifed two bone-related pathways, one involving “osteoclast differentiation” and the other the “MAPK signaling pathway.” These results may help us better understand the molecular mechanism of bone traits in chickens and other birds and provide new insights for the genetic breeding of chickens.
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Affiliation(s)
- Zhihao Zhang
- Institute of Animal Sciences, Chinese Academy of Agricultural Science, Beijing, China
| | - Weifang Yang
- Beijing General Station of Animal Husbandry, Beijing, China
| | - Tao Zhu
- State Key Laboratory of Animal Nutrition, Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Liang Wang
- Beijing General Station of Animal Husbandry, Beijing, China
| | - Xiaoyu Zhao
- Hebei Dawu Poultry Breeding Co., Ltd., Hebei, China
| | | | - Lujiang Qu
- State Key Laboratory of Animal Nutrition, Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
- *Correspondence: Lujiang Qu, ; Yaxiong Jia,
| | - Yaxiong Jia
- Institute of Animal Sciences, Chinese Academy of Agricultural Science, Beijing, China
- *Correspondence: Lujiang Qu, ; Yaxiong Jia,
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Frangi G, Guicheteau M, Jacquot F, Pyka G, Kerckhofs G, Feyeux M, Veziers J, Guihard P, Halgand B, Sourice S, Guicheux J, Prieur X, Beck L, Beck-Cormier S. PiT2 deficiency prevents increase of bone marrow adipose tissue during skeletal maturation but not in OVX-induced osteoporosis. Front Endocrinol (Lausanne) 2022; 13:921073. [PMID: 36465661 PMCID: PMC9708882 DOI: 10.3389/fendo.2022.921073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 10/24/2022] [Indexed: 11/17/2022] Open
Abstract
The common cellular origin between bone marrow adipocytes (BMAds) and osteoblasts contributes to the intimate link between bone marrow adipose tissue (BMAT) and skeletal health. An imbalance between the differentiation ability of BMSCs towards one of the two lineages occurs in conditions like aging or osteoporosis, where bone mass is decreased. Recently, we showed that the sodium-phosphate co-transporter PiT2/SLC20A2 is an important determinant for bone mineralization, strength and quality. Since bone mass is reduced in homozygous mutant mice, we investigated in this study whether the BMAT was also affected in PiT2-/- mice by assessing the effect of the absence of PiT2 on BMAT volume between 3 and 16 weeks, as well as in an ovariectomy-induced bone loss model. Here we show that the absence of PiT2 in juveniles leads to an increase in the BMAT that does not originate from an increased adipogenic differentiation of bone marrow stromal cells. We show that although PiT2-/- mice have higher BMAT volume than control PiT2+/+ mice at 3 weeks of age, BMAT volume do not increase from 3 to 16 weeks of age, leading to a lower BMAT volume in 16-week-old PiT2-/- compared to PiT2+/+ mice. In contrast, the absence of PiT2 does not prevent the increase in BMAT volume in a model of ovariectomy-induced bone loss. Our data identify SLC20a2/PiT2 as a novel gene essential for the maintenance of the BMAd pool in adult mice, involving mechanisms of action that remain to be elucidated, but which appear to be independent of the balance between osteoblastic and adipogenic differentiation of BMSCs.
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Affiliation(s)
- Giulia Frangi
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Marie Guicheteau
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Frederic Jacquot
- Nantes Université, CHU Nantes, Inserm, CNRS, CRCI2NA, Nantes, France
| | - Grzegorz Pyka
- Biomechanics lab, Institute of Mechanics, Materials, and Civil Engineering, UC Louvain, Louvain-la-Neuve, Belgium
- Department of Materials Engineering, KU Leuven, Leuven, Belgium
| | - Greet Kerckhofs
- Biomechanics lab, Institute of Mechanics, Materials, and Civil Engineering, UC Louvain, Louvain-la-Neuve, Belgium
- Department of Materials Engineering, KU Leuven, Leuven, Belgium
- IREC, Institute of Experimental and Clinical Research, UC Louvain, Woluwé-Saint-Lambert, Belgium
- Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
| | - Magalie Feyeux
- Nantes Université, CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, Nantes, France
| | - Joëlle Veziers
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Pierre Guihard
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Boris Halgand
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Sophie Sourice
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Jérôme Guicheux
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Xavier Prieur
- Nantes Université, CNRS, Inserm, l’Institut du Thorax, Nantes, France
| | - Laurent Beck
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
| | - Sarah Beck-Cormier
- Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton, RMeS, UMR 1229, SFR Bonamy, Nantes, France
- *Correspondence: Sarah Beck-Cormier,
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13
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Zhang S, Lyons N, Koedam M, van de Peppel J, van Leeuwen JP, van der Eerden BCJ. Identification of small molecules as novel anti-adipogenic compounds based on Connectivity Map. Front Endocrinol (Lausanne) 2022; 13:1017832. [PMID: 36589834 PMCID: PMC9800878 DOI: 10.3389/fendo.2022.1017832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 11/29/2022] [Indexed: 12/23/2022] Open
Abstract
Several physiological and pathological conditions such as aging, obesity, diabetes, anorexia nervosa are associated with increased adipogenesis in the bone marrow. A lack of effective drugs hinder the improved treatment for aberrant accumulation of bone marrow adipocytes. Given the higher costs, longer duration and sometimes lack of efficacy in drug discovery, computational and experimental strategies have been used to identify previously approved drugs for the treatment of diseases, also known as drug repurposing. Here, we describe the method of small molecule-prioritization by employing adipocyte-specific genes using the connectivity map (CMap). We then generated transcriptomic profiles using human mesenchymal stromal cells under adipogenic differentiation with the treatment of prioritized compounds, and identified emetine and kinetin-riboside to have a potent inhibitory effect on adipogenesis. Overall, we demonstrated a proof-of-concept method to identify repurposable drugs capable of inhibiting adipogenesis, using the Connectivity Map.
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Affiliation(s)
- Shuang Zhang
- Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Nicholas Lyons
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
| | - Marijke Koedam
- Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Jeroen van de Peppel
- Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Johannes P.T.M. van Leeuwen
- Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Bram C. J. van der Eerden
- Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands
- *Correspondence: Bram C. J. van der Eerden,
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14
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Zheng CS, Wen HQ, Lin WS, Luo XW, Shen LS, Zhou X, Zou FY, Li QL, Hu HJ, Guo RM. Quantification of lumbar vertebral fat deposition: Correlation with menopausal status, non-alcoholic fatty liver disease and subcutaneous adipose tissue. Front Endocrinol (Lausanne) 2022; 13:1099919. [PMID: 36714601 PMCID: PMC9878446 DOI: 10.3389/fendo.2022.1099919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 12/27/2022] [Indexed: 01/15/2023] Open
Abstract
PURPOSE To assess abdominal fat deposition and lumbar vertebra with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) and investigate their correlation with menopausal status. MATERIALS AND METHODS Two hundred forty women who underwent routine abdominal MRI and IDEAL-IQ between January 2016 and April 2021 were divided into two cohorts (first cohort: 120 pre- or postmenopausal women with severe fatty livers or without fatty livers; second cohort: 120 pre- or postmenopausal women who were obese or normal weight). The fat fraction (FF) values of the liver (FFliver) and lumbar vertebra (FFlumbar) in the first group and the FF values of subcutaneous adipose tissue (SAT) (FFSAT) and FFlumbar in the second group were measured and compared using IDEAL-IQ. RESULTS Two hundred forty women were evaluated. FFlumbar was significantly higher in both pre- and postmenopausal women with severe fatty liver than in patients without fatty livers (premenopausal women: p < 0.001, postmenopausal women: p < 0.001). No significant difference in the FFlumbar was observed between obese patients and normal-weight patients among pre- and postmenopausal women (premenopausal women: p = 0.113, postmenopausal women: p = 0.092). Significantly greater lumbar fat deposition was observed in postmenopausal women than in premenopausal women with or without fatty liver and obesity (p < 0.001 for each group). A high correlation was detected between FFliver and FFlumbar in women with severe fatty liver (premenopausal women: r=0.76, p<0.01; postmenopausal women: r=0.82, p<0.01). CONCLUSION Fat deposition in the vertebral marrow was significantly associated with liver fat deposition in postmenopausal women.
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Affiliation(s)
- Chu-Shan Zheng
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hui-Quan Wen
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wu-Sheng Lin
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiao-Wen Luo
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li-Shan Shen
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiang Zhou
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Feng-Yun Zou
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qing-Ling Li
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of VIP Medical Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Qing-Ling Li, ; Hui-Jun Hu, ; Ruo-Mi Guo,
| | - Hui-Jun Hu
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Qing-Ling Li, ; Hui-Jun Hu, ; Ruo-Mi Guo,
| | - Ruo-Mi Guo
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- *Correspondence: Qing-Ling Li, ; Hui-Jun Hu, ; Ruo-Mi Guo,
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15
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Chang HK, Hsu TW, Ku J, Ku J, Wu JC, Lirng JF, Hsu SM. Simple parameters of synthetic MRI for assessment of bone density in patients with spinal degenerative disease. J Neurosurg Spine 2021:1-8. [PMID: 34653988 DOI: 10.3171/2021.6.spine21666] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/10/2021] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Good bone quality is the key to avoiding osteoporotic fragility fractures and poor outcomes after lumbar instrumentation and fusion surgery. Although dual-energy x-ray absorptiometry (DEXA) screening is the current standard for evaluating osteoporosis, many patients lack DEXA measurements before undergoing lumbar spine surgery. The present study aimed to investigate the utility of using simple quantitative parameters generated with novel synthetic MRI to evaluate bone quality, as well as the correlations of these parameters with DEXA measurements. METHODS This prospective study enrolled patients with symptomatic lumbar degenerative disease who underwent DEXA and conventional and synthetic MRI. The quantitative parameters generated with synthetic MRI were T1 map, T2 map, T1 intensity, proton density (PD), and vertebral bone quality (VBQ) score, and these parameters were correlated with T-score of the lumbar spine. RESULTS There were 62 patients and 238 lumbar segments eligible for analysis. PD and VBQ score moderately correlated with T-score of the lumbar spine (r = -0.565 and -0.651, respectively; both p < 0.001). T1 intensity correlated fairly well with T-score (r = -0.411, p < 0.001). T1 and T2 correlated poorly with T-score. Receiver operating characteristic curve analysis demonstrated area under the curve values of 0.808 and 0.794 for detecting osteopenia/osteoporosis (T-score ≤ -1.0) and osteoporosis (T-score ≤ -2.5) with PD (both p < 0.001). CONCLUSIONS PD and T1 intensity values generated with synthetic MRI demonstrated significant correlation with T-score. PD has excellent ability for predicting osteoporosis and osteopenia.
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Affiliation(s)
- Hsuan-Kan Chang
- 1Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.,2College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,3Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tun-Wei Hsu
- 4Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.,5Integrated PET/MR Imaging Center, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Johnson Ku
- 6University of California, Los Angeles, California; and
| | - Jason Ku
- 6University of California, Los Angeles, California; and
| | - Jau-Ching Wu
- 2College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,3Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.,7Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jiing-Feng Lirng
- 2College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,4Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shih-Ming Hsu
- 1Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
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16
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Li Z, MacDougald OA. Preclinical models for investigating how bone marrow adipocytes influence bone and hematopoietic cellularity. Best Pract Res Clin Endocrinol Metab 2021; 35:101547. [PMID: 34016532 PMCID: PMC8458229 DOI: 10.1016/j.beem.2021.101547] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Laboratory mice are a crucial preclinical model system for investigating bone marrow adipocyte (BMAd)-bone and BMAd-hematopoiesis interactions. In this review, we evaluate the suitability of mice to model common human diseases related to osteopenia or hematopoietic disorders, point out consistencies and discrepancies among different studies, and provide insights into model selection. Species, age, sex, skeletal site, and treatment protocol should all be considered when designing future studies.
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Affiliation(s)
- Ziru Li
- Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Ormond A MacDougald
- Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
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17
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Abstract
Research examining bone marrow adipose tissue (BMAT) has rapidly expanded during the last two decades, leading to advances in knowledge on the role of BMAT in the pathogenesis of bone loss and endocrine disorders. Clinical imaging has played a crucial role for the in vivo assessment of BMAT, allowing non-invasive quantification and evaluation of BMAT composition. In the present work, we review different imaging methods for assessing properties of BMAT. Our aim is to review conventional magnetic resonance imaging (MRI), water-fat imaging, and single-voxel proton magnetic resonance spectroscopy (1H-MRS), as well as computed tomography (CT)-based techniques, including single energy and dual energy CT. We will also discuss the clinical applications of these methods in type 2 diabetes mellitus, obesity and anorexia nervosa.
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Affiliation(s)
- Mohamed Jarraya
- Massachusetts General Hospital, Department of Radiology, Harvard Medical School, Boston, MA, USA.
| | - Miriam A Bredella
- Massachusetts General Hospital, Department of Radiology, Harvard Medical School, Boston, MA, USA
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18
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Zhang Y, Chen Y, Sun H, Zhang W, Zhang L, Li H, Huang X, Yang J, Ye Z. SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis. Front Cell Dev Biol 2021; 9:693079. [PMID: 34249943 PMCID: PMC8266396 DOI: 10.3389/fcell.2021.693079] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 05/26/2021] [Indexed: 12/23/2022] Open
Abstract
Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis and reduced bone formation was the main pathological change in GIOP. Our previous studies have shown that there was an imbalance between adipogenic and osteogenic differentiation in GIOP BM-MSCs and peroxisome proliferator-activated receptor γ2 (PPARγ2) played a vital role in this disorders. Here, we reported that there was an increase in ROS level and SENP3 expression in Dex-induced osteoporotic BM-MSCs, and enhanced adipogenesis and weakened osteogenesis in osteoporotic BM-MSCs might be caused by upregulated SENP3. Then we found that SENP3 de-SUMOylated PPARγ2 on K107 site to potentiate adipogenesis and weaken osteogenesis. These results may provide new strategy and target in the clinical diagnosis and treatment of GIOP.
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Affiliation(s)
- Yongxing Zhang
- Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institute of Orthopedic Research, Zhejiang University, Hangzhou, China.,Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yang Chen
- Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hangxiang Sun
- Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institute of Orthopedic Research, Zhejiang University, Hangzhou, China
| | - Wenkan Zhang
- Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institute of Orthopedic Research, Zhejiang University, Hangzhou, China
| | - Lingling Zhang
- Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institute of Orthopedic Research, Zhejiang University, Hangzhou, China
| | - Hengyuan Li
- Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institute of Orthopedic Research, Zhejiang University, Hangzhou, China
| | - Xin Huang
- Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institute of Orthopedic Research, Zhejiang University, Hangzhou, China
| | - Jie Yang
- Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhaoming Ye
- Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institute of Orthopedic Research, Zhejiang University, Hangzhou, China
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19
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Chun LF, Yu EL, Sawh MC, Bross C, Nichols J, Polgreen L, Knott C, Schlein A, Sirlin CB, Middleton MS, Kado DM, Schwimmer JB. Hepatic Steatosis is Negatively Associated with Bone Mineral Density in Children. J Pediatr 2021; 233:105-111.e3. [PMID: 33545191 PMCID: PMC8154638 DOI: 10.1016/j.jpeds.2021.01.064] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/12/2021] [Accepted: 01/27/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To evaluate the relationship between hepatic steatosis and bone mineral density (BMD) in children. In addition, to assess 25-hydroxyvitamin D levels in the relationship between hepatic steatosis and BMD. STUDY DESIGN A community-based sample of 235 children was assessed for hepatic steatosis, BMD, and serum 25-hydroxyvitamin D. Hepatic steatosis was measured by liver magnetic resonance imaging proton density fat fraction (MRI-PDFF). BMD was measured by whole-body dual-energy x-ray absorptiometry. RESULTS The mean age of the study population was 12.5 years (SD 2.5 years). Liver MRI-PDFF ranged from 1.1% to 40.1% with a mean of 9.3% (SD 8.5%). Across this broad spectrum of hepatic fat content, there was a significant negative relationship between liver MRI-PDFF and BMD z score (R = -0.421, P < .001). Across the states of sufficiency, insufficiency, and deficiency, there was a significant negative association between 25-hydroxyvitamin D and liver MRI-PDFF (P < .05); however, there was no significant association between vitamin D status and BMD z score (P = .94). Finally, children with clinically low BMD z scores were found to have higher alanine aminotransferase (P < .05) and gamma-glutamyl transferase (P < .05) levels compared with children with normal BMD z scores. CONCLUSIONS Across the full range of liver MRI-PDFF, there was a strong negative relationship between hepatic steatosis and BMD z score. Given the prevalence of nonalcoholic fatty liver disease and the critical importance of childhood bone mineralization in protecting against osteoporosis, clinicians should prioritize supporting bone development in children with nonalcoholic fatty liver disease.
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Affiliation(s)
- Lauren F. Chun
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California
| | - Elizabeth L. Yu
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California,Department of Gastroenterology, Rady Children’s Hospital, San Diego, California
| | - Mary Catherine Sawh
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California,Department of Gastroenterology, Rady Children’s Hospital, San Diego, California
| | - Craig Bross
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California
| | - Jeanne Nichols
- Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California,Graduate School of Public Health, San Diego State University, San Diego, California
| | - Lynda Polgreen
- Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California
| | - Cynthia Knott
- Altman Clinical and Translational Research Institute, School of Medicine, University of California San Diego School of Medicine, Ja Jolla, California
| | - Alexandra Schlein
- Liver Imaging Group, Department of Radiology, University of California San Diego School of Medicine, La Jolla, California
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of California San Diego School of Medicine, La Jolla, California
| | - Michael S. Middleton
- Liver Imaging Group, Department of Radiology, University of California San Diego School of Medicine, La Jolla, California
| | - Deborah M. Kado
- Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California,Department of Internal Medicine, University of California San Diego, La Jolla, California
| | - Jeffrey B. Schwimmer
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California San Diego School of Medicine, La Jolla, California,Department of Gastroenterology, Rady Children’s Hospital, San Diego, California
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20
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Fonseca H, Bezerra A, Coelho A, Duarte JA. Association between Visceral and Bone Marrow Adipose Tissue and Bone Quality in Sedentary and Physically Active Ovariectomized Wistar Rats. Life (Basel) 2021; 11:life11060478. [PMID: 34070279 PMCID: PMC8225130 DOI: 10.3390/life11060478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 05/20/2021] [Accepted: 05/21/2021] [Indexed: 01/13/2023] Open
Abstract
Background: Obesity is considered protective for bone mass, but this view has been progressively challenged. Menopause is characterized by low bone mass and increased adiposity. Our aim was to determine how visceral and bone marrow adiposity change following ovariectomy (OVX), how they correlate with bone quality and if they are influenced by physical activity. Methods: Five-month-old Wistar rats were OVX or sham-operated and maintained in sedentary or physically active conditions for 9 months. Visceral and bone marrow adiposity as well as bone turnover, femur bone quality and biomechanical properties were assessed. Results: OVX resulted in higher weight, visceral and bone marrow adiposity. Visceral adiposity correlated inversely with femur Ct.Th (r = −0.63, p < 0.001), BV/TV (r = −0.67, p < 0.001), Tb.N (r = −0.69, p < 0.001) and positively with Tb.Sp (r = 0.58, p < 0.001). Bone marrow adiposity also correlated with bone resorption (r = 0.47, p < 0.01), bone formation rate (r = −0.63, p < 0.01), BV/TV (r = −0.85, p < 0.001), Ct.Th (r = −0.51, p < 0.0.01), and with higher empty osteocyte lacunae (r = 0.39, p < 0.05), higher percentage of osteocytes with oxidative stress (r = 0.64, p < 0.0.01) and lower femur maximal stress (r = −0.58, p < 0.001). Physical activity correlated inversely with both visceral (r = −0.74, p < 0.01) and bone marrow adiposity (r = −0.92, p < 0.001). Conclusions: OVX increases visceral and bone marrow adiposity which are associated with inferior bone quality and biomechanical properties. Physical activity could contribute to reduce adipose tissue and thereby improve bone quality.
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Affiliation(s)
- Hélder Fonseca
- Faculty of Sport, University of Porto (FADE/UP), 4200-450 Porto, Portugal; (A.B.); (A.C.); (J.A.D.)
- Research Center of Physical Activity, Health and Leisure (CIAFEL), 4200-450 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
- Correspondence: ; Tel.: +351-220-425-239
| | - Andrea Bezerra
- Faculty of Sport, University of Porto (FADE/UP), 4200-450 Porto, Portugal; (A.B.); (A.C.); (J.A.D.)
- Research Center of Physical Activity, Health and Leisure (CIAFEL), 4200-450 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
| | - Ana Coelho
- Faculty of Sport, University of Porto (FADE/UP), 4200-450 Porto, Portugal; (A.B.); (A.C.); (J.A.D.)
- Research Center of Physical Activity, Health and Leisure (CIAFEL), 4200-450 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
| | - José Alberto Duarte
- Faculty of Sport, University of Porto (FADE/UP), 4200-450 Porto, Portugal; (A.B.); (A.C.); (J.A.D.)
- Research Center of Physical Activity, Health and Leisure (CIAFEL), 4200-450 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
- Polytechnic and University Higher Education Cooperative (CESPU), 4485-116 Gandra Campus, 4050-600 Porto, Portugal
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Singhal V, Karzar NH, Bose A, Buckless C, Ackerman KE, Bredella MA, Klibanski A, Misra M. Changes in marrow adipose tissue in relation to changes in bone parameters following estradiol replacement in adolescent and young adult females with functional hypothalamic amenorrhea. Bone 2021; 145:115841. [PMID: 33418100 PMCID: PMC8022869 DOI: 10.1016/j.bone.2021.115841] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 12/14/2020] [Accepted: 01/01/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol administration in physiologic doses increases BMD in adolescents and adults with FHA. However, the impact of estrogen replacement on MAT in relation to changes in BMD has not been studied in adolescents and young adults. We hypothesized that physiologic estrogen replacement would lead to decreases in MAT, associated with increases in BMD. METHODS AND MATERIALS We studied 15 adolescent and young adult females with FHA (14-25 years). All participants received a17β- estradiol transdermal patch at a dose of 0.1 mg/day (applied twice weekly) for 12 months. Participants also received cyclic progestin for 10-12 days each month. We quantified MAT (lipid/water ratio) of the fourth lumbar (L4) vertebral body and femoral diaphysis by single proton (1H)-magnetic resonance spectroscopy, and compartmental volumetric BMD of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. RESULTS Transdermal estradiol therapy over 12 months resulted in a decrease in MAT at the lumbar (L4) vertebra from 0.92 ± 0.55 at baseline to 0.63 ± 0.29 at 12-months (p = 0.008), and an increase in radial and tibial cortical vBMD (p = 0.006, p = 0.0003). Changes in L4 MAT trended to be inversely associated with changes in radial cortical vBMD (rho = -0.47, p = 0.08). CONCLUSION We show that in adolescent and young adult girls with FHA, MAT decreases following transdermal estrogen therapy and these changes are associated with increased cortical vBMD.
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Affiliation(s)
- Vibha Singhal
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Division of Pediatric Endocrinology, Mass General Hospital for Children and Harvard Medical School, Boston, MA, United States; MGH Weight Center, Massachusetts General Hospital, Boston, MA, United States.
| | - Nazanin Hazhir Karzar
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
| | - Amita Bose
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
| | - Colleen Buckless
- Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
| | - Kathryn E Ackerman
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
| | - Miriam A Bredella
- Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
| | - Anne Klibanski
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
| | - Madhusmita Misra
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Division of Pediatric Endocrinology, Mass General Hospital for Children and Harvard Medical School, Boston, MA, United States.
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22
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Zhang Y, Yang K, Yang J, Lao Y, Deng L, Deng G, Yi J, Sun X, Wang Q. SENP3 Suppresses Osteoclastogenesis by De-conjugating SUMO2/3 from IRF8 in Bone Marrow-Derived Monocytes. Cell Rep 2021; 30:1951-1963.e4. [PMID: 32049023 DOI: 10.1016/j.celrep.2020.01.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 11/19/2019] [Accepted: 01/09/2020] [Indexed: 10/25/2022] Open
Abstract
Bone metabolism depends on the balance between osteoclast-driven bone resorption and osteoblast-mediated bone formation. Diseases like osteoporosis are characterized by increased bone destruction due to partially enhanced osteoclastogenesis. Here, we report that the post-translational SUMO modification is critical for regulating osteoclastogenesis. The expression of the SUMO-specific protease SENP3 is downregulated in osteoclast precursors during osteoclast differentiation. Mice with SENP3 deficiency in bone marrow-derived monocytes (BMDMs) exhibit more severe bone loss due to over-activation of osteoclasts after ovariectomy. Deleting SENP3 in BMDMs promotes osteoclast differentiation. Mechanistically, loss of SENP3 increases interferon regulatory factor 8 (IRF8) SUMO3 modification at the K310 amino acid site, which upregulates expression of the nuclear factor of activated T cell c1 (NFATc1) and osteoclastogenesis. In summary, IRF8 de-SUMO modification mediated by SENP3 suppresses osteoclast differentiation and suggests strategies to treat bone loss diseases.
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Affiliation(s)
- Yongxing Zhang
- Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Kai Yang
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jie Yang
- Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yimin Lao
- Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Lianfu Deng
- Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Guoying Deng
- Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
| | - Jing Yi
- Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Xuxu Sun
- Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Qiugen Wang
- Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
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23
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Whitney DG, Alford AI, Devlin MJ, Li Y, Caird MS. Intersite reliability of vertebral bone marrow lipidomics-derived lipid composition among children with varying degrees of bone fragility undergoing routine orthopedic surgery. Bone 2021; 143:115633. [PMID: 32927104 PMCID: PMC7770023 DOI: 10.1016/j.bone.2020.115633] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/30/2020] [Accepted: 09/09/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND Lipidomics, a branch of metabolomics, is an attractive technique to characterize bone marrow lipid composition, which may be associated with skeletal acquisition and homeostasis. However, the reliability of lipidomics-derived lipid composition of the bone marrow is unknown, especially for pediatric populations with bone fragility. The purpose of this study was to evaluate the intersite reliability and standard error of measurement (SEM) of vertebral bone marrow lipid composition at the thoracic (T11/T12) and lumbar (L1/L2) spine determined by targeted lipidomics among children with varying degrees of bone fragility undergoing routine orthopedic surgery. METHODS Children aged between 12 and 19 years of age, with a confirmed diagnosis of adolescent idiopathic scoliosis or neuromuscular scoliosis and cerebral palsy, and undergoing routine posterior spinal fusion surgery at our institution were initially included in this study. Transpedicular vertebral body bone marrow samples were taken from thoracic (T) or lumbar (L) vertebrae. Further inclusion criteria involved having bone marrow extracted from both T11 and T12 (n = 24) or L1 and L2 (n = 19). Lipid composition was measured using a targeted lipidomics technique and examined as the saturated, monounsaturated, and polyunsaturated index and as individual fatty acids. Relative and absolute test-retest reliability was assessed using the intraclass correlation coefficient (ICC) and SEM. RESULTS For the T11/T12 analysis: the ICC and SEM were 0.59 and 1.7% for the saturated index, 0.31 and 6.2% for the monounsaturated index, and 0.44 and 6.1% for the polyunsaturated index; the ICC showed a considerable range for individual fatty acids from 0.07 (fatty acid 20:2) to 0.82 (15:0) with 62.1% of the fatty acids having poor reliability (i.e., ICC < 0.50). For the L1/L2 analysis: the ICC and SEM were 0.50 and 2.4% for the saturated index, -0.12 and 6.0% for the monounsaturated index, and 0.00 and 4.9% for the polyunsaturated index; the ICC showed a considerable range for individual fatty acids from -0.34 (18:1_n-9) to 0.88 (15:0 and 18:3_n-3) with 79.3% of the fatty acids having poor reliability. CONCLUSIONS The intersite test-retest reliability was poor-to-moderate for index measures and generally poor for individual fatty acids for the thoracic and lumbar spine. At this time, it is not recommended to pool bone marrow adipose tissue across vertebral sites for bone marrow adiposity research or clinical monitoring for pediatric populations with bone fragility.
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Affiliation(s)
- Daniel G Whitney
- Department of Physical Medicine and Rehabilitation, University of Michigan, 325 E. Eisenhower, Ann Arbor, MI 48108, United States of America; Institute for Healthcare Policy and Innovation, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109, United States of America.
| | - Andrea I Alford
- Department of Orthopaedic Surgery, University of Michigan, A. Alfred Taubman Biomedical Sciences Research Building, Room 2009, Ann Arbor, MI 48109, United States of America
| | - Maureen J Devlin
- Department of Anthropology, University of Michigan, 1085 S. University Ave., Ann Arbor, MI 48109, United States of America
| | - Ying Li
- Department of Orthopaedic Surgery, University of Michigan, A. Alfred Taubman Biomedical Sciences Research Building, Room 2009, Ann Arbor, MI 48109, United States of America
| | - Michelle S Caird
- Department of Orthopaedic Surgery, University of Michigan, A. Alfred Taubman Biomedical Sciences Research Building, Room 2009, Ann Arbor, MI 48109, United States of America
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24
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Whitney DG, Devlin MJ, Alford AI, Caird MS. Pattern of bone marrow lipid composition measures along the vertebral column: A descriptive study of adolescents with idiopathic scoliosis. Bone 2021; 142:115702. [PMID: 33099030 PMCID: PMC9426858 DOI: 10.1016/j.bone.2020.115702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/03/2020] [Accepted: 10/18/2020] [Indexed: 11/21/2022]
Abstract
BACKGROUND There is evidence that the extent of vertebral bone marrow adiposity increases caudally along the vertebral column in children and adolescents. However, no studies have examined the lipid composition of bone marrow along the vertebral column, which may uniquely influence bone acquisition and metabolism during growth independent of the amount of bone marrow adipose tissue. The goal of this study was to characterize the pattern of lipid composition index measures from the thoracic to lumbar spine (T11-L4) among a sample of adolescents with idiopathic scoliosis (AIS) undergoing routine orthopedic surgical care for scoliosis correction. METHODS Adolescents between 14 and 18 years of age, with a confirmed diagnosis of AIS, and undergoing routine posterior spinal fusion surgery at our institution were initially included for this descriptive study. The surgery yielded transpedicular vertebral body marrow samples from T11 through L4; 11 participants had bone marrow samples from T11 through L2 and 4 of the 11 participants had marrow samples from T11 through L4. Lipid composition index measures, including the saturated, monounsaturated, and polyunsaturated index, were measured using a targeted lipidomics technique. Linear regression equation for the slope (m) and Pearson correlation coefficient (r) was computed to assess the pattern of lipid composition index measures along the vertebral column from T11 to L2 (n = 11) and extended analysis to L4. Exploratory analyses were performed to examine the association between the pattern of lipid composition measures (individual slopes) and physical characteristics for T11-L2. RESULTS For T11-L2, the slope of the saturated index was near 0 (r = 0.08; P = 0.92), whereas the slopes of the unsaturated indices were approximately opposite of one another: the monounsaturated index exhibited a -0.55 change (r = 0.58; P = 0.42) per vertebra and the polyunsaturated index exhibited a 0.52 change (r = 0.72; P = 0.28) per vertebra in the caudal direction from T11-L2. For T11-L4, there were modest changes in slope for the saturated (m = 0.12; r = 0.30; P = 0.57) and monounsaturated (m = -0.68; r = 0.74; P = 0.09) indices, while the polyunsaturated index slope remained similar (m = 0.56; r = 0.89; P = 0.02). Age, sex, height, body mass, and BMI were not associated with the pattern of any of the lipid composition index measures. CONCLUSIONS Study findings in this small sample of individuals with AIS suggest that the bone marrow saturated index may be relatively stable across T11-L4, while the monounsaturated index may decrease by 0.55-0.68% per vertebra and the polyunsaturated index may increase by 0.52-0.56% per vertebra in the caudal direction.
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Affiliation(s)
- Daniel G Whitney
- Department of Physical Medicine and Rehabilitation, University of Michigan, 325 E. Eisenhower, Ann Arbor, MI 48108, United States of America; Institute for Healthcare Policy and Innovation, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109, United States of America.
| | - Maureen J Devlin
- Department of Anthropology, University of Michigan, 1085 S. University Ave., Ann Arbor, MI 48109, United States of America
| | - Andrea I Alford
- Department of Orthopaedic Surgery, University of Michigan, A. Alfred Taubman Biomedical Sciences Research Building, Room 2009, Ann Arbor, MI 48109, United States of America
| | - Michelle S Caird
- Department of Orthopaedic Surgery, University of Michigan, A. Alfred Taubman Biomedical Sciences Research Building, Room 2009, Ann Arbor, MI 48109, United States of America
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25
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Whitney DG, Devlin MJ, Alford AI, Modlesky CM, Peterson MD, Li Y, Caird MS. Test-Retest Reliability and Correlates of Vertebral Bone Marrow Lipid Composition by Lipidomics Among Children With Varying Degrees of Bone Fragility. JBMR Plus 2020; 4:e10400. [PMID: 33103029 PMCID: PMC7574707 DOI: 10.1002/jbm4.10400] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/01/2020] [Accepted: 07/20/2020] [Indexed: 12/22/2022] Open
Abstract
The reliability of lipidomics, an approach to identify the presence and interactions of lipids, to analyze the bone marrow lipid composition among pediatric populations with bone fragility is unknown. The objective of this study was to assess the test–retest reliability, standard error of measurement (SEM), and the minimal detectable change (MDC) of vertebral bone marrow lipid composition determined by targeted lipidomics among children with varying degrees of bone fragility undergoing routine orthopedic surgery. Children aged 10 to 19 years, with a confirmed diagnosis of adolescent idiopathic scoliosis (n = 13) or neuromuscular scoliosis and cerebral palsy (n = 3), undergoing posterior spinal fusion surgery at our institution were included in this study. Transpedicular vertebral body bone marrow samples were taken from thoracic vertebrae (T11, 12) or lumbar vertebrae (L1 to L4). Lipid composition was assessed via targeted lipidomics and all samples were analyzed in the same batch. Lipid composition measures were examined as the saturated, monounsaturated, and polyunsaturated index and as individual fatty acids. Relative and absolute test–retest reliability was assessed using the intraclass correlation coefficient (ICC), SEM, and MDC. Associations between demographics and index measures were explored. The ICC, SEM, and MDC were 0.81 (95% CI, 0.55–0.93), 1.6%, and 4.3%, respectively, for the saturated index, 0.66 (95% CI, 0.25–0.87), 3.5%, and 9.7%, respectively, for the monounsaturated index, and 0.60 (95% CI, 0.17–0.84), 3.6%, and 9.9%, respectively, for the polyunsaturated index. For the individual fatty acids, the ICC showed a considerable range from 0.04 (22:2n‐6) to 0.97 (18:3n‐3). Age was positively correlated with the saturated index (r2 = 0.36; p = 0.014) and negatively correlated with the polyunsaturated index (r2 = 0.26; p = 0.043); there was no difference in index measures by sex (p > 0.58). The test–retest reliability was moderate‐to‐good for index measures and poor to excellent for individual fatty acids; this information can be used to power research studies and identify measures for clinical or research monitoring. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Daniel G Whitney
- Department of Physical Medicine and Rehabilitation University of Michigan Ann Arbor MI USA.,Institute for Healthcare Policy and Innovation University of Michigan Ann Arbor MI USA
| | - Maureen J Devlin
- Department of Anthropology University of Michigan Ann Arbor MI USA
| | - Andrea I Alford
- Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA
| | | | - Mark D Peterson
- Department of Physical Medicine and Rehabilitation University of Michigan Ann Arbor MI USA.,Institute for Healthcare Policy and Innovation University of Michigan Ann Arbor MI USA
| | - Ying Li
- Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA
| | - Michelle S Caird
- Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA
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26
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Aparisi Gómez MP, Ayuso Benavent C, Simoni P, Aparisi F, Guglielmi G, Bazzocchi A. Fat and bone: the multiperspective analysis of a close relationship. Quant Imaging Med Surg 2020; 10:1614-1635. [PMID: 32742956 DOI: 10.21037/qims.2020.01.11] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The study of bone has for many years been focused on the study of its mineralized component, and one of the main objects of study as radiology developed as a medical specialty. The assessment has until recently been almost limited to its role as principal component of the scaffolding of the human body. Bone is a very active tissue, in continuous cross-talk with other organs and systems, with functions that are endocrine and paracrine and that have an important involvement in metabolism, ageing and health in general. Bone is also the continent for the bone marrow, in the form of "yellow marrow" (mainly adipocytes) or "red marrow" (hematopoietic cells and adipocytes). Recently, numerous studies have focused on these adipocytes contained in the bone marrow, often referred to as marrow adipose tissue (MAT). Bone marrow adipocytes do not only work as storage tissue, but are also endocrine and paracrine cells, with the potential to contribute to local bone homeostasis and systemic metabolism. Many metabolic disorders (osteoporosis, obesity, diabetes) have a complex and still not well-established relationship with MAT. The development of imaging methods, in particular the development of cross-sectional imaging has helped us to understand how much more laid beyond our classical way to look at bone. The impact on the mineralized component of bone in some cases (e.g., osteoporosis) is well-established, and has been extensively analyzed and quantified through different radiological methods. The application of advanced magnetic resonance techniques has unlocked the possibility to access the detailed study, characterization and quantification of the bone marrow components in a non-invasive way. In this review, we will address what is the evidence on the physiological role of MAT in normal skeletal health (interaction with the other bone components), during the process of normal aging and in the context of some metabolic disorders, highlighting the role that imaging methods play in helping with quantification and diagnosis.
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Affiliation(s)
- Maria Pilar Aparisi Gómez
- Department of Radiology, Auckland City Hospital, Auckland, New Zealand.,Department of Radiology, Hospital Vithas Nueve de Octubre, Valencia, Spain
| | | | - Paolo Simoni
- Department of Radiology, "Reine Fabiola" Children's University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Francisco Aparisi
- Department of Radiology, Hospital Vithas Nueve de Octubre, Valencia, Spain
| | - Giuseppe Guglielmi
- Department of Radiology, University of Foggia, Foggia, Italy.,Department of Radiology, Hospital San Giovanni Rotondo, Foggia, Italy
| | - Alberto Bazzocchi
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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27
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Al Saedi A, Chen L, Phu S, Vogrin S, Miao D, Ferland G, Gaudreau P, Duque G. Age-Related Increases in Marrow Fat Volumes have Regional Impacts on Bone Cell Numbers and Structure. Calcif Tissue Int 2020; 107:126-134. [PMID: 32356017 DOI: 10.1007/s00223-020-00700-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 04/21/2020] [Indexed: 01/08/2023]
Abstract
The increasing levels of bone marrow fat evident in aging and osteoporosis are associated with low bone mass and attributed to reduced osteoblastogenesis. Local lipotoxicity has been proposed as the primary mechanism driving this reduction in bone formation. However, no studies have examined the correlation between high levels of marrow fat volumes and changes in local cellularity. In this study, we hypothesize that areas of bone marrow with high fat volumes are associated with significant changes in cell number within a similar region of interest (ROI). Inbred albino Louvain (LOU) rats, originating from the Wistar strain, have been described as a model of healthy aging with the absence of obesity but expressing the typical features of age-related bone loss. We compared local changes in distal femur cellularity and structure in specific ROI of undecalcified bone sections from 4- and 20-month-old male and female LOU rats and Wistar controls. Our results confirmed that older LOU rats exhibited significantly higher fat volumes than Wistar rats (p < 0.001). These higher fat volume/total volume were associated with lower trabecular number (p < 0.05) and thickness (p < 0.05) and higher trabecular separation (p < 0.05). In addition, osteoblast and osteocyte numbers were reduced in the similar ROI containing high levels of adiposity, while osteoclast number was higher compared to control (p < 0.03). In summary, marrow ROIs with a high level of adiposity were associated with a lower bone mass and changes in cellularity explaining associated bone loss. Further studies assessing the levels of lipotoxicity in areas of high local marrow adiposity and identifying molecular actors involved in this phenomenon are still required.
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Affiliation(s)
- Ahmed Al Saedi
- Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, 176 Furlong Road, St. Albans, VIC, 3021, Australia
- Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia
| | - Lulu Chen
- Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, 176 Furlong Road, St. Albans, VIC, 3021, Australia
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Steven Phu
- Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, 176 Furlong Road, St. Albans, VIC, 3021, Australia
- Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia
| | - Sara Vogrin
- Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia
| | - Dengshun Miao
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Guylaine Ferland
- Département de Nutrition, Faculté de médecine de l'université de Montréal (UdeM) and Centre de Recherche de L'Institut de Cardiologie de Montréal, Montréal, QC, Canada
| | - Pierrette Gaudreau
- Département de médecine, UdeM and Laboratoire de Neuroendocrinologie du Vieillissement, Centre de Recherche du Centre Hospitalier de l'université de Montreal (UdeM), 900 rue Saint-Denis, Pavillon R, Montréal, QC, Canada
| | - Gustavo Duque
- Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, 176 Furlong Road, St. Albans, VIC, 3021, Australia.
- Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia.
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28
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Suchacki KJ, Tavares AAS, Mattiucci D, Scheller EL, Papanastasiou G, Gray C, Sinton MC, Ramage LE, McDougald WA, Lovdel A, Sulston RJ, Thomas BJ, Nicholson BM, Drake AJ, Alcaide-Corral CJ, Said D, Poloni A, Cinti S, Macpherson GJ, Dweck MR, Andrews JPM, Williams MC, Wallace RJ, van Beek EJR, MacDougald OA, Morton NM, Stimson RH, Cawthorn WP. Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. Nat Commun 2020; 11:3097. [PMID: 32555194 PMCID: PMC7303125 DOI: 10.1038/s41467-020-16878-2] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 05/29/2020] [Indexed: 12/30/2022] Open
Abstract
Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype.
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Affiliation(s)
- Karla J Suchacki
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Adriana A S Tavares
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Domenico Mattiucci
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
- Dipartimento di Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
| | - Erica L Scheller
- Division of Bone and Mineral Diseases, Department of Medicine, Washington University, St. Louis, MO, USA
| | | | - Calum Gray
- Edinburgh Imaging, University of Edinburgh, Edinburgh, UK
| | - Matthew C Sinton
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Lynne E Ramage
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Wendy A McDougald
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Andrea Lovdel
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Richard J Sulston
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Benjamin J Thomas
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Bonnie M Nicholson
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Amanda J Drake
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Carlos J Alcaide-Corral
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Diana Said
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Antonella Poloni
- Dipartimento di Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
| | - Saverio Cinti
- Dipartimento di Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy
- Dipartimento di Medicina Sperimentale e Clinica, Center of Obesity, Università Politecnica delle Marche, Ancona, Italy
| | - Gavin J Macpherson
- Department of Orthopaedic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Marc R Dweck
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Jack P M Andrews
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Michelle C Williams
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Robert J Wallace
- Department of Orthopaedics, The University of Edinburgh, Edinburgh, UK
| | | | - Ormond A MacDougald
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
| | - Nicholas M Morton
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Roland H Stimson
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - William P Cawthorn
- University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
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Yu C, Peall IW, Pham SH, Okolicsanyi RK, Griffiths LR, Haupt LM. Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance. Int J Mol Sci 2020; 21:ijms21113884. [PMID: 32485953 PMCID: PMC7312587 DOI: 10.3390/ijms21113884] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/27/2020] [Accepted: 05/27/2020] [Indexed: 12/20/2022] Open
Abstract
Bone marrow-derived human mesenchymal stems cells (hMSCs) are precursors to adipocyte and osteoblast lineage cells. Dysregulation of the osteo-adipogenic balance has been implicated in pathological conditions involving bone loss. Heparan sulfate proteoglycans (HSPGs) such as cell membrane-bound syndecans (SDCs) and glypicans (GPCs) mediate hMSC lineage differentiation and with syndecan-1 (SDC-1) reported in both adipogenesis and osteogenesis, these macromolecules are potential regulators of the osteo-adipogenic balance. Here, we disrupted the HSPG profile in primary hMSC cultures via temporal knockdown (KD) of SDC-1 using RNA interference (RNAi) in undifferentiated, osteogenic and adipogenic differentiated hMSCs. SDC-1 KD cultures were examined for osteogenic and adipogenic lineage markers along with changes in HSPG profile and common signalling pathways implicated in hMSC lineage fate. Undifferentiated hMSC SDC-1 KD cultures exhibited a pro-adipogenic phenotype with subsequent osteogenic differentiation demonstrating enhanced maturation of osteoblasts. In cultures where SDC-1 KD was performed following initiation of differentiation, increased adipogenic gene and protein marker expression along with increased Oil Red O staining identified enhanced adipogenesis, with impaired osteogenesis also observed in these cultures. These findings implicate SDC-1 as a facilitator of the hMSC osteo-adipogenic balance during early induction of lineage differentiation.
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Hua KC, Feng JT, Yang XG, Wang F, Zhang H, Yang L, Zhang HR, Xu MY, Li JK, Qiao RQ, Lun DX, Hu YC. Assessment of the Defatting Efficacy of Mechanical and Chemical Treatment for Allograft Cancellous Bone and Its Effects on Biomechanics Properties of Bone. Orthop Surg 2020; 12:617-630. [PMID: 32189444 PMCID: PMC7189055 DOI: 10.1111/os.12639] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 01/30/2020] [Indexed: 11/29/2022] Open
Abstract
Objective To assess the defatting efficacy of high pressure washing and gradient alcohol and biomechanical properties of defatted bone. Methods Fresh cancellous bone was obtained from the femoral condyle and divided into six groups according to different defatting treatments, which were: high pressure washing for 10 s (10S group), 20 s (20S group), and 30 s (30S group), gradient alcohol immersion (Alcohol group), acetone immersion (Acetone group), and non‐defatted (Fresh group). The appearance of six groups was observed, and the appearance of defatted bone and fresh bone was compared. The residual lipid content and infrared spectrum were used to compare the efficacy of defatting, the DNA content was used to compare the cell content after defatting, and the maximum stress and elastic modulus were used to compare the effects of defatting treatment on biomechanical properties. Results The fresh bone was yellow and the pores contained a lot of fat. The defatted bone was white and the porous network was clear. There was no difference in residual lipid content among the three groups with high pressure washing (1.45% ± 0.16%, 1.40% ± 0.13%, and 1.46% ± 0.11%, respectively) (P = 0.828). There was no difference in residual lipid content among the 10S, alcohol, and acetone groups (1.45% ± 0.16%, 1.28% ± 0.07%, and 1.13% ± 0.22%, respectively) (P = 0.125). Infrared spectra showed that the fat content of the five defatting groups was significantly lower than that of the fresh group. There was no difference in residual lipid content among the three groups with high pressure washing (4.53 ± 0.23 ug/mL, 4.61 ± 0.18 ug/mL, and 4.66 ± 0.25 ug/mL, respectively) (P = 0.645). There was no difference in residual lipid content among the 10S, alcohol, and acetone groups (4.53 ± 0.23 ug/mL, 4.29 ± 0.24 ug/mL, and 4.27 ± 0.29 ug/mL, respectively) (P = 0.247). The maximum stress of the bone decreased significantly with the increase of the washing time (9.95 ± 0.31 Mpa, 9.07 ± 0.45 Mpa, and 8.17 ± 0.35 Mpa, respectively) (P = 0.003). The elastic modulus of the bone decreased significantly with the increase of the washing time (116.40 ± 3.54 Mpa, 106.10 ± 5.29 Mpa, and 95.63 ± 4.08 Mpa, respectively) (P = 0.003). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group, and the acetone group (10.09 ± 0.67 Mpa, 9.95 ± 0.31 Mpa, 10.11 ± 0.07 Mpa, and 10.09 ± 0.39 Mpa, respectively) (P = 0.963). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group and the acetone group (119.93 ± 4.94 Mpa, 116.40 ± 3.54 Mpa, 118.27 ± 0.85 Mpa, 118.10 ± 4.52 Mpa, respectively) (P = 0.737). Conclusion The defatting efficiency was satisfactory at a time of 10 s under high pressure washing. In terms of defatting efficiency and its effect on biomechanical properties of bone, high pressure washing and gradient alcohol were similar to conventional acetone solvent extraction defatting.
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Affiliation(s)
- Kun-Chi Hua
- Department of Bone Tumor, Tianjin Hospital, Tianjin, China.,Graduate School, Tianjin Medical University, Tianjin, China
| | - Jiang-Tao Feng
- Graduate School, Tianjin Medical University, Tianjin, China
| | | | - Feng Wang
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Hao Zhang
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Li Yang
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Hao-Ran Zhang
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Ming-You Xu
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Ji-Kai Li
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Rui-Qi Qiao
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Deng-Xing Lun
- Deng-xing Lun, MD, Department of Spine Surgery, Weifang People's Hospital, Weifang, China
| | - Yong-Cheng Hu
- Department of Bone Tumor, Tianjin Hospital, Tianjin, China
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31
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Bone marrow fat fraction assessment in regard to physical activity: KORA FF4-3-T MR imaging in a population-based cohort. Eur Radiol 2020; 30:3417-3428. [PMID: 32086579 DOI: 10.1007/s00330-019-06612-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 10/31/2019] [Accepted: 12/06/2019] [Indexed: 01/03/2023]
Abstract
OBJECTIVES To establish the effect of different degrees and kinds of physical activity on bone marrow fat (BMAT) content at different anatomical locations in a population-based cohort study undergoing whole-body MR imaging. METHODS Subjects of the KORA FF4 study without known cardiovascular disease underwent BMAT fat fraction (FF) quantification in L1 and L2 vertebrae and femoral heads/necks (hip) via a 2-point T1-weighted VIBE Dixon sequence. BMAT-FF was calculated as mean value (fat image) divided by mean value (fat + water image). Physical activity was determined by self-assessment questionnaire regarding time spent exercising, non-exercise walking, non-exercise cycling, and job-related physical activity. RESULTS A total of 385 subjects (96% of 400 available; 56 ± 9.1 years; 58% male) were included in the analysis. Exercise was distributed quite evenly (29% > 2 h/week; 31% ~ 1 h/week (regularly); 15% ~ 1 h/week (irregularly); 26% no physical activity). BMAT-FF was 52.6 ± 10.2% in L1, 56.2 ± 10.3% in L2, 87.4 ± 5.9% in the right hip, and 87.2 ± 5.9% in the left hip (all p < 0.001). Correlation of BMAT-FF between spine and hip was only moderate (r 0.42 to 0.46). Spinal BMAT-FF, but not hip BMAT-FF, was inversely associated with exercise > 2 h/week (p ≤ 0.02 vs. p ≥ 0.35, respectively). These associations remained significant after adjusting for age, gender, waist circumference, and glucose tolerance. No coherent association was found between BMAT-FF and physical activity in the less active groups. CONCLUSIONS In our study, exercise was inversely correlated with vertebral BMAT-FF, but not hip BMAT-FF, when exercising for more than 2 h per week. Physical activity seems to affect the spine at least preferentially compared to the hip. KEY POINTS • In our population-based cohort, at least 2 h of physical activity per week were required to show lower levels of bone marrow adipose tissue fat fraction in MRI. • Physical activity seems to affect bone marrow adipose tissue at least preferentially at the spine in contrast to the proximal femur.
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Abstract
PURPOSE OF REVIEW The age-related accumulation of bone marrow adipose tissue (BMAT) negatively impacts bone metabolism and hematopoiesis. This review provides an overview about BMAT-secreted factors as biomarkers for BMAT accumulation and osteoporosis risk. RECENT FINDINGS The adipokines leptin and adiponectin are regulators of BMAT. It remains to be clarified if locally produced adipokines substantially contribute to their peripheral serum levels and if they influence bone metabolism beyond that of extraosseous adipokine production. Existing data also suggests that BMAT disturbs bone metabolism primarily through palmitate-mediated toxic effects on osteoblasts and osteocytes, including dysregulated autophagy and apoptosis. BMAT-secreted factors are important modulators of bone metabolism. However, the majority of our understanding about MAT-secreted factors and their paracrine and endocrine effects is derived from in vitro studies and animal experiments. Therefore, more research is needed before BMAT-secreted biomarkers can be applied in medical practice.
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Affiliation(s)
- Markus Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15/1, 8036, Graz, Austria.
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Baraghithy S, Smoum R, Attar-Namdar M, Mechoulam R, Bab I, Tam J. HU-671, a Novel Oleoyl Serine Derivative, Exhibits Enhanced Efficacy in Reversing Ovariectomy-Induced Osteoporosis and Bone Marrow Adiposity. Molecules 2019; 24:molecules24203719. [PMID: 31623098 PMCID: PMC6832161 DOI: 10.3390/molecules24203719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 10/05/2019] [Accepted: 10/15/2019] [Indexed: 01/06/2023] Open
Abstract
Oleoyl serine (OS), an endogenous fatty acyl amide (FAA) found in bone, has been shown to have an anti-osteoporotic effect. OS, being an amide, can be hydrolyzed in the body by amidases. Hindering its amide bond by introducing adjacent substituents has been demonstrated as a successful method for prolonging its skeletal activity. Here, we tested the therapeutic efficacy of two methylated OS derivatives, oleoyl α-methyl serine (HU-671) and 2-methyl-oleoyl serine (HU-681), in an ovariectomized mouse model for osteoporosis by utilizing combined micro-computed tomography, histomorphometry, and cell culture analyses. Our findings indicate that daily treatment for 6 weeks with OS or HU-671 completely rescues bone loss, whereas HU-681 has only a partial effect. The increased bone density was primarily due to enhanced trabecular thickness and number. Moreover, the most effective dose of HU-671 was 0.5 mg/kg/day, an order of magnitude lower than with OS. The reversal of bone loss resulted from increased bone formation and decreased bone resorption, as well as reversal of bone marrow adiposity. These results were further confirmed by determining the serum levels of osteocalcin and type 1 collagen C-terminal crosslinks, as well as demonstrating the enhanced antiadipogenic effect of HU-671. Taken together, these data suggest that methylation interferes with OS’s metabolism, thus enhancing its effects by extending its availability to its target cells.
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Affiliation(s)
- Saja Baraghithy
- Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel;
- Bone Laboratory, Institute for Dental Research, Faculty of Dentistry, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel; (R.S.)
| | - Reem Smoum
- Bone Laboratory, Institute for Dental Research, Faculty of Dentistry, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel; (R.S.)
- Medicinal Chemistry Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel;
| | - Malka Attar-Namdar
- Bone Laboratory, Institute for Dental Research, Faculty of Dentistry, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel; (R.S.)
| | - Raphael Mechoulam
- Medicinal Chemistry Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel;
| | - Itai Bab
- Bone Laboratory, Institute for Dental Research, Faculty of Dentistry, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel; (R.S.)
| | - Joseph Tam
- Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel;
- Correspondence: ; Tel.: +972-2-6757645; Fax: +972-2-6757015
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Sebo ZL, Rendina-Ruedy E, Ables GP, Lindskog DM, Rodeheffer MS, Fazeli PK, Horowitz MC. Bone Marrow Adiposity: Basic and Clinical Implications. Endocr Rev 2019; 40:1187-1206. [PMID: 31127816 PMCID: PMC6686755 DOI: 10.1210/er.2018-00138] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 04/03/2019] [Indexed: 12/14/2022]
Abstract
The presence of adipocytes in mammalian bone marrow (BM) has been recognized histologically for decades, yet, until recently, these cells have received little attention from the research community. Advancements in mouse transgenics and imaging methods, particularly in the last 10 years, have permitted more detailed examinations of marrow adipocytes than ever before and yielded data that show these cells are critical regulators of the BM microenvironment and whole-body metabolism. Indeed, marrow adipocytes are anatomically and functionally separate from brown, beige, and classic white adipocytes. Thus, areas of BM space populated by adipocytes can be considered distinct fat depots and are collectively referred to as marrow adipose tissue (MAT) in this review. In the proceeding text, we focus on the developmental origin and physiologic functions of MAT. We also discuss the signals that cause the accumulation and loss of marrow adipocytes and the ability of these cells to regulate other cell lineages in the BM. Last, we consider roles for MAT in human physiology and disease.
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Affiliation(s)
- Zachary L Sebo
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.,Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut
| | | | - Gene P Ables
- Orentreich Foundation for the Advancement of Science, Cold Spring, New York
| | - Dieter M Lindskog
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut
| | - Matthew S Rodeheffer
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.,Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut
| | - Pouneh K Fazeli
- Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts
| | - Mark C Horowitz
- Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut
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35
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Bone Marrow Fat Physiology in Relation to Skeletal Metabolism and Cardiometabolic Disease Risk in Children With Cerebral Palsy. Am J Phys Med Rehabil 2019; 97:911-919. [PMID: 29894311 DOI: 10.1097/phm.0000000000000981] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Individuals with cerebral palsy exhibit neuromuscular complications and low physical activity levels. Adults with cerebral palsy exhibit a high prevalence of chronic diseases, which is associated with musculoskeletal deficits. Children with cerebral palsy have poor musculoskeletal accretion accompanied by excess bone marrow fat, which may lead to weaker bones. Mechanistic studies to determine the role of bone marrow fat on skeletal growth and maintenance and how it relates to systemic energy metabolism among individuals with cerebral palsy are lacking. In this review, we highlight the skeletal status in children with cerebral palsy and analyze the existing literature on the interactions among bone marrow fat, skeletal health, and cardiometabolic disease risk in the general population. Clinically vital questions are proposed, including the following: (1) Is the bone marrow fat in children with cerebral palsy metabolically distinct from typically developing children in terms of its lipid and inflammatory composition? (2) Does the bone marrow fat suppress skeletal acquisition? (3) Or, does it accelerate chronic disease development in children with cerebral palsy? (4) If so, what are the mechanisms? In conclusion, although inadequate mechanical loading may initiate poor skeletal development, subsequent expansion of bone marrow fat may further impede skeletal acquisition and increase cardiometabolic disease risk in those with cerebral palsy.
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36
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Esche J, Shi L, Hartmann MF, Schönau E, Wudy SA, Remer T. Glucocorticoids and Body Fat Inversely Associate With Bone Marrow Density of the Distal Radius in Healthy Youths. J Clin Endocrinol Metab 2019; 104:2250-2256. [PMID: 30715368 DOI: 10.1210/jc.2018-02108] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 01/25/2019] [Indexed: 01/28/2023]
Abstract
CONTEXT Elevated bone marrow adipose tissue (BMAT) is associated with lower bone quality, higher fracture rates, and an unfavorable overall metabolic profile. Apart from age, particularly glucocorticoids (GC), body fat, and diet are discussed to influence BMAT. We hypothesized that already in healthy youths, higher fat intake, higher fat mass index (FMI), and higher GC secretion, still within the normal range, may associate with increased BMAT. DESIGN In a subsample of healthy 6- to 18-year-old participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, peripheral quantitative CT of the nondominant proximal forearm was used to determine bone marrow density of the distal radius as an inverse surrogate parameter for BMAT. In those participants (n = 172) who had collected two, 24-hour urines within around one year before bone measurement, major urinary GC metabolites were measured by gas chromatography-mass spectrometry and summed up to assess daily adrenal GC secretion (ΣC21). Dietary intake was assessed by 3-day weighed dietary records. FMI was anthropometrically calculated. Separate multiple linear regression models were used to analyze the relationships of ΣC21, FMI, and fat intake with BMAT. RESULTS After controlling for confounders, such as age, energy intake, and forearm muscle area, ΣC21 (β = -0.042) and FMI (β = -0.002) showed inverse relationships with bone marrow density (P < 0.05), whereas fat intake did not associate significantly. CONCLUSION Our results indicate that already a moderately elevated GC secretion and higher body fatness during adolescence may adversely impact BMAT, an indicator for long-term bone health.
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Affiliation(s)
- Jonas Esche
- Dortmund Nutritional and Anthropometric Longitudinally Designed Study Center, Institute of Nutrition and Food Science, Nutritional Epidemiology, University of Bonn, Dortmund, Germany
| | - Lijie Shi
- Dortmund Nutritional and Anthropometric Longitudinally Designed Study Center, Institute of Nutrition and Food Science, Nutritional Epidemiology, University of Bonn, Dortmund, Germany
| | - Michaela F Hartmann
- Steroid Research and Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus-Liebig-University, Giessen, Germany
| | - Eckhard Schönau
- Children's Hospital, University of Cologne, Cologne, Germany
| | - Stefan A Wudy
- Steroid Research and Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus-Liebig-University, Giessen, Germany
| | - Thomas Remer
- Dortmund Nutritional and Anthropometric Longitudinally Designed Study Center, Institute of Nutrition and Food Science, Nutritional Epidemiology, University of Bonn, Dortmund, Germany
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37
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Dimitri P. The Impact of Childhood Obesity on Skeletal Health and Development. J Obes Metab Syndr 2019; 28:4-17. [PMID: 31089575 PMCID: PMC6484936 DOI: 10.7570/jomes.2019.28.1.4] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 01/24/2019] [Accepted: 02/18/2019] [Indexed: 12/26/2022] Open
Abstract
Increased risk of fracture identified in obese children has led to a focus on the relationship between fat, bone, and the impact of obesity during skeletal development. Early studies have suggested that despite increased fracture risk, obese children have a higher bone mass. However, body size corrections applied to account for wide variations in size between children led to the finding that obese children have a lower total body and regional bone mass relative to their body size. Advances in skeletal imaging have shifted the focus from quantity of bone in obese children to evaluating the changes in bone microarchitecture that result in a change in bone quality and strength. The findings suggest that bone strength in the appendicular skeleton does not appropriately adapt to an increase in body size which results in a mismatch between bone strength and force from falls. Recent evidence points to differing influences of fat compartments on skeletal development-visceral fat may have a negative impact on bone which may be related to the associated adverse metabolic environment, while marrow adipose tissue may have an independent effect on trabecular bone development in obese children. The role of brown fat has received recent attention, demonstrating differences in the influence on bone mass between white and brown adipose tissues. Obesity results in a shift in growth and pubertal hormones as well as influences bone development through the altered release of adipokines. The change in the hormonal milieu provides an important insight into the skeletal changes observed in childhood obesity.
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Affiliation(s)
- Paul Dimitri
- Academic Unit of Child Health, The University of Sheffield, Sheffield, UK
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38
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Fazeli PK, Faje AT, Bredella MA, Polineni S, Russell S, Resulaj M, Rosen CJ, Klibanski A. Changes in marrow adipose tissue with short-term changes in weight in premenopausal women with anorexia nervosa. Eur J Endocrinol 2019; 180:189-199. [PMID: 30566901 PMCID: PMC6545162 DOI: 10.1530/eje-18-0824] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 12/18/2018] [Indexed: 01/19/2023]
Abstract
OBJECTIVE In anorexia nervosa, a psychiatric disease characterized by self-induced starvation and a model of chronic undernutrition, levels of subcutaneous (SAT) and visceral (VAT) adipose tissue are low, whereas marrow adipose tissue (MAT) levels are elevated compared to normal-weight women. The reason for this paradoxical elevation of an adipose tissue depot in starvation is not known. We sought to understand changes in MAT in response to subacute changes in weight and to compare these changes with those of other fat depots and body composition parameters. DESIGN AND METHODS We conducted a 12-month longitudinal study including 46 premenopausal women (n = 26 with anorexia nervosa and n = 20 normal-weight controls) with a mean (s.e.m.) age of 28.2 ± 0.8 years. We measured MAT, SAT, VAT and bone mineral density (BMD) at baseline and after 12 months. RESULTS At baseline, SAT (P < 0.0001), VAT (P < 0.02) and BMD of the spine and hip (P ≤ 0.0002) were significantly lower and vertebral and metaphyseal MAT (P ≤ 0.001) significantly higher in anorexia nervosa compared to controls. Weight gain over 12 months was associated with increases not only in SAT and VAT, but also epiphyseal MAT (P < 0.03). Changes in epiphyseal MAT were positively associated with changes in BMD (P < 0.03). CONCLUSIONS In contrast to the steady state, in which MAT levels are higher in anorexia nervosa and MAT and BMD are inversely associated, short-term weight gain is associated with increases in both MAT and BMD. These longitudinal data demonstrate the dynamic nature of this fat depot and provide further evidence of its possible role in mineral metabolism.
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Affiliation(s)
- Pouneh K. Fazeli
- Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Alexander T. Faje
- Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Miriam A. Bredella
- Department of Radiology, Massachusetts General Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Sai Polineni
- Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA
| | - Stephen Russell
- Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA
| | - Megi Resulaj
- Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA
| | | | - Anne Klibanski
- Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA
- Harvard Medical School, Boston, MA
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39
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Chandra A, Park SS, Pignolo RJ. Potential role of senescence in radiation-induced damage of the aged skeleton. Bone 2019; 120:423-431. [PMID: 30543989 DOI: 10.1016/j.bone.2018.12.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 12/04/2018] [Accepted: 12/08/2018] [Indexed: 12/21/2022]
Abstract
Human aging-related changes are exacerbated in cases of disease and cancer, and conversely aging is a catalyst for the occurrence of disease and multimorbidity. For example, old age is the most significant risk factor for cancer and among people who suffer from cancer, >60% are above the age of 65. Oxidative stress and DNA damage, leading to genomic instability and telomere dysfunction, are prevalent in aging and radiation-induced damage and are major cellular events that lead to senescence. Human exposures from nuclear fallout, cosmic radiation and clinical radiotherapy (RT) are some common sources of irradiation that affect bone tissue. RT has been used to treat malignant tumors for over a century, but the effects of radiation damage on tumor-adjacent normal tissue has largely been overlooked. There is an increase in the percent survivorship among patients post-RT, and it is in older survivors where the deleterious synergy between aging and radiation exposure conspires to promote tissue deterioration and dysfunction which then negatively impacts their quality of life. Thus, an aging skeleton is already pre-disposed to architectural deterioration, which is further worsened by radiation-induced bone damage. Effects of senescence and the senescence associated secretory phenotype (SASP) have been implicated in age-associated bone loss, but their roles in radiation-associated bone damage are still elusive. RT is used in treatment for a variety of cancers and in different anatomical locations, the sequelae of which include long-term morbidity and lifelong discomfort. Therefore, consideration of the growing evidence that implicates the role of senescence in radiation-induced bone damage argues in favor of exploiting current senotherapeutic approaches as a possible prevention or treatment.
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Affiliation(s)
- Abhishek Chandra
- Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA.
| | - Sean S Park
- Department of Radiation Oncology, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Robert J Pignolo
- Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA.
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40
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Abstract
Bone strength is affected not only by bone mineral density (BMD) and bone microarchitecture but also its microenvironment. Recent studies have focused on the role of marrow adipose tissue (MAT) in the pathogenesis of bone loss. Osteoblasts and adipocytes arise from a common mesenchymal stem cell within bone marrow and many osteoporotic states, including aging, medication use, immobility, over - and undernutrition are associated with increased marrow adiposity. Advancements in imaging technology allow the non-invasive quantification of MAT. This article will review magnetic resonance imaging (MRI)- and computed tomography (CT)-based imaging technologies to assess the amount and composition of MAT. The techniques that will be discussed are anatomic T1-weighted MRI, water-fat imaging, proton MR spectroscopy, single energy CT and dual energy CT. Clinical applications of MRI and CT techniques to determine the role of MAT in patients with obesity, anorexia nervosa, and type 2 diabetes will be reviewed.
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Affiliation(s)
- Vibha Singhal
- Pediatric Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Miriam A Bredella
- Department of Radiology, Musculoskeletal Imaging and Interventions, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States.
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41
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Li Y, Meng Y, Yu X. The Unique Metabolic Characteristics of Bone Marrow Adipose Tissue. Front Endocrinol (Lausanne) 2019; 10:69. [PMID: 30800100 PMCID: PMC6375842 DOI: 10.3389/fendo.2019.00069] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 01/24/2019] [Indexed: 02/05/2023] Open
Abstract
Bone marrow adipose tissue (MAT) is distinct from white adipose tissue (WAT) or brown adipose tissue (BAT) for its location, feature and function. As a largely ignored adipose depot, it is situated in bone marrow space and resided with bone tissue side-by-side. MAT is considered not only as a regulator of bone metabolism through paracrine, but also as a functionally particular adipose tissue that may contribute to global metabolism. Adipokines, inflammatory factors and other molecules derived from bone marrow adipocytes may exert systematic effects. In this review, we summary the evidence from several aspects including development, distribution, histological features and phenotype to elaborate the basic characteristics of MAT. We discuss the association between bone metabolism and MAT, and highlight our current understanding of this special adipose tissue. We further demonstrate the probable relationship between MAT and energy metabolism, as well as glucose metabolism. On the basis of preliminary results from animal model and clinical studies, we propose that MAT has its unique secretory and metabolic function, although there is no in-depth study at present.
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Affiliation(s)
- Yujue Li
- Laboratory of Endocrinology and Metabolism, Department of Endocrinology and Metabolism and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Yang Meng
- Laboratory of Endocrinology and Metabolism, Department of Endocrinology and Metabolism and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China
| | - Xijie Yu
- Laboratory of Endocrinology and Metabolism, Department of Endocrinology and Metabolism and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xijie Yu ;
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42
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Fazeli PK, Klibanski A. The paradox of marrow adipose tissue in anorexia nervosa. Bone 2019; 118:47-52. [PMID: 29458121 PMCID: PMC6095826 DOI: 10.1016/j.bone.2018.02.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 02/13/2018] [Accepted: 02/14/2018] [Indexed: 12/19/2022]
Abstract
Anorexia nervosa (AN) is a psychiatric disorder characterized by inappropriate nutrient intake resulting in low body weight. Multiple hormonal adaptations facilitate decreased energy expenditure in this state of caloric deprivation including non-thyroidal illness syndrome, growth hormone resistance, and hypogonadotropic hypogonadism. Although these hormonal adaptations confer a survival advantage during periods of negative energy balance, they contribute to the long-term medical complications associated with AN, the most common of which is significant bone loss and an increased risk of fracture. In recent years, marrow adipose tissue (MAT) has emerged as an important potential determinant of the low bone mass state characteristic of AN. Unlike subcutaneous and visceral adipose tissue depots which are low in AN, MAT levels are paradoxically elevated and are inversely associated with BMD. In this review, we discuss what is known about MAT in AN and the proposed hormonal determinants of this adipose tissue depot.
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Affiliation(s)
- Pouneh K Fazeli
- Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
| | - Anne Klibanski
- Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
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43
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Zhu M, Hao G, Xing J, Hu S, Geng D, Zhang W, Wang Q, Hu C, Wang X. Bone marrow adipose amount influences vertebral bone strength. Exp Ther Med 2018; 17:689-694. [PMID: 30651851 PMCID: PMC6307407 DOI: 10.3892/etm.2018.7003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 11/08/2018] [Indexed: 11/06/2022] Open
Abstract
Association of bone marrow adipose and microstructure with bone strength in osteoporotic rats using MR Dixon analysis and micro-CT was evaluated. A total of 40 female Sprague-Dawley rats (6-month-old) were divided randomly into sham-operated (SHAM, n=20) group and ovariectomized (OVX, n=20) group. Fat fraction (FF) was measured by two-point Dixon method with MR imaging at the baseline, 4th, 8th and 12th week, respectively. After sacrifice by anesthesia, the fifth lumbar vertebrae bone was sampled for micro-CT scanning. The biomechanical analysis was also performed. FF in osteoporotic rats significantly increases with time, which correlates with bone microstructure parameters. Compared with biomechanical test, FF showed negative correlation with break stress and elastic modulus. It also suggested that loss of bone mass was accompanied with the increase of adipose tissue content in vertebrae bone marrow. The impairment of bone strength leads to the risk of brittle fracture. In conclusion, the bone marrow adipose amount obtained by MR Dixon and microstructure by micro-CT correlates to bone strength in osteoporotic rats.
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Affiliation(s)
- Mo Zhu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Guangyu Hao
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Jianming Xing
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Su Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Dechun Geng
- Department of Orthopedic, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Wen Zhang
- Department of Orthopedic, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Qianqian Wang
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Chunhong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
| | - Ximing Wang
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
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44
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Abstract
Bone marrow adipocytes (BMA-) constitute an original and heterogeneous fat depot whose development appears interlinked with bone status throughout life. The gradual replacement of the haematopoietic tissue by BMA arises in a well-ordered way during childhood and adolescence concomitantly to bone growth and continues at a slower rate throughout the adult life. Importantly, BM adiposity quantity is found well associated with bone mineral density (BMD) loss at different skeletal sites in primary osteoporosis such as in ageing or menopause but also in secondary osteoporosis consecutive to anorexia nervosa. Since BMA and osteoblasts originate from a common mesenchymal stem cell, adipogenesis is considered as a competitive process that disrupts osteoblastogenesis. Besides, most factors secreted by bone and bone marrow cells (ligands and antagonists of the WNT/β-catenin pathway, BMP and others) reciprocally regulate the two processes. Hormones such as oestrogens, glucocorticoids, parathyroid and growth hormones that control bone remodelling also modulate the differentiation and the activity of BMA. Actually, BMA could also contribute to bone loss through the release of paracrine factors altering osteoblast and/or osteoclast formation and function. Based on clinical and fundamental studies, this review aims at presenting and discussing these current arguments that support but also challenge the involvement of BMA in the bone mass integrity.
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Affiliation(s)
- Tareck Rharass
- Littoral Côte d’Opale University, Lille University, EA 4490, PMOI, Physiopathologie des Maladies Osseuses Inflammatoires, Lille, F-59000, France
| | - Stéphanie Lucas
- Littoral Côte d’Opale University, Lille University, EA 4490, PMOI, Physiopathologie des Maladies Osseuses Inflammatoires, Lille, F-59000, France
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45
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Di Iorgi N, Maruca K, Patti G, Mora S. Update on bone density measurements and their interpretation in children and adolescents. Best Pract Res Clin Endocrinol Metab 2018; 32:477-498. [PMID: 30086870 DOI: 10.1016/j.beem.2018.06.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Following the increased awareness about the central role of the pediatric age in building bone for life, clinicians face more than ever the necessity of assessing bone health in pediatric subjects at risk for early bone mass derangements or in healthy children, in order to optimize their bone mass accrual and prevent osteoporosis. Although the diagnosis of osteoporosis is not made solely upon bone mineral density measurements during growth, such determination can be very useful in the follow-up of pediatric patients with primary and secondary osteoporosis. The ideal instrument would give information on the mineral content and density of the bone, and on its architecture. It should be able to perform the measurements on the skeletal sites where fractures are more frequent, and it should be minimally invasive, accurate, precise and rapid. Unfortunately, none of the techniques currently utilized fulfills all requirements. In the present review, we focus on the pediatric use of dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), peripheral QCT (pQCT), and magnetic resonance imaging (MRI), highlighting advantages and limits for their use and providing indications for bone densitometry interpretation and of vertebral fractures diagnosis in pediatric subjects.
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Affiliation(s)
- Natascia Di Iorgi
- Department of Pediatrics, Istituto Giannina Gaslini, University of Genova, Genova, Italy.
| | - Katia Maruca
- Pediatric Bone Densitormetry Service and Laboratory of Pediatric Endocrinology, IRCCS San Raffaele Institute, Milano, Italy
| | - Giuseppa Patti
- Department of Pediatrics, Istituto Giannina Gaslini, University of Genova, Genova, Italy
| | - Stefano Mora
- Pediatric Bone Densitormetry Service and Laboratory of Pediatric Endocrinology, IRCCS San Raffaele Institute, Milano, Italy.
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46
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Coutel X, Olejnik C, Marchandise P, Delattre J, Béhal H, Kerckhofs G, Penel G. A Novel microCT Method for Bone and Marrow Adipose Tissue Alignment Identifies Key Differences Between Mandible and Tibia in Rats. Calcif Tissue Int 2018; 103:189-197. [PMID: 29383407 DOI: 10.1007/s00223-018-0397-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 01/24/2018] [Indexed: 12/11/2022]
Abstract
Bone homeostasis is influenced by the bone marrow adipose tissue (BMAT). BMAT distribution varies from one anatomical location in the skeleton to another. We developed an advanced microfocus computed tomography imaging and analysis protocol that allows accurate alignment of both the BMAT distribution and bone micro-architecture as well as calculation of the distance of the BMAT adipocytes from the bone surface. Using this protocol, we detected a different spatial BMAT distribution between the rat tibia and mandible: in the proximal metaphysis of the tibia a large amount of BMAT (~ 20% of the total BMAT) was located close to the bone surface (< 20 µm), whereas in the alveolar ridge ~ 30% of the total BMAT was located between 40 and 60 µm from the bone surface. In the alveolar ridge of rats, the trabecular bone volume was 48.3% higher compared to the proximal metaphysis of the tibia (p < 0.0001) and the percentage of adiposity determined to the relative marrow volume was lower (1.5%) compared to the proximal metaphysis of the tibia (9%, p = 0.0002). Interestingly, in the tibia a negative correlation was found between the percentage of adiposity in the total volume and the trabecular thickness (r =- 0.74, p = 0.037). The present study highlights that in comparison to tibial proximal metaphysis, the mandibular bone exhibits a massive trabecular network and a low BMAT content with almost no contact with the bone surface. These findings are of great interest because of the importance of the fat-bone interaction and its potential relevance to several resorptive bone diseases.
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Affiliation(s)
- Xavier Coutel
- Univ.Lille, Univ. Littoral Côte d'Opale, EA 4490 - PMOI - Physiopathologie des Maladies Osseuses Inflammatoires, 59000, Lille, France.
| | - Cécile Olejnik
- Univ.Lille, Univ. Littoral Côte d'Opale, EA 4490 - PMOI - Physiopathologie des Maladies Osseuses Inflammatoires, 59000, Lille, France
| | - Pierre Marchandise
- Univ.Lille, Univ. Littoral Côte d'Opale, EA 4490 - PMOI - Physiopathologie des Maladies Osseuses Inflammatoires, 59000, Lille, France
| | - Jérôme Delattre
- Univ.Lille, Univ. Littoral Côte d'Opale, EA 4490 - PMOI - Physiopathologie des Maladies Osseuses Inflammatoires, 59000, Lille, France
| | - Hélène Béhal
- Univ. Lille, CHU Lille, EA 2694 - Santé publique: épidémiologie et qualité des soins, Unité de Méthodologie et Biostatistiques, 59000, Lille, France
| | - Greet Kerckhofs
- Department of Development and Regeneration, Skeletal Biology and Engineering Center, KU Leuven, Leuven, Belgium
- Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
| | - Guillaume Penel
- Univ.Lille, Univ. Littoral Côte d'Opale, EA 4490 - PMOI - Physiopathologie des Maladies Osseuses Inflammatoires, 59000, Lille, France
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47
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Cao JJ. Caloric restriction combined with exercise is effective in reducing adiposity and mitigating bone structural deterioration in obese rats. Ann N Y Acad Sci 2018; 1433:41-52. [DOI: 10.1111/nyas.13936] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 06/27/2018] [Accepted: 06/29/2018] [Indexed: 12/21/2022]
Affiliation(s)
- Jay J. Cao
- USDA, Agricultural Research Service Grand Forks Human Nutrition Research Center Grand Forks North Dakota
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48
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Vajapeyam S, Ecklund K, Mulkern RV, Feldman HA, O'Donnell JM, DiVasta AD, Rosen CJ, Gordon CM. Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa. Bone 2018; 110:335-342. [PMID: 29496516 PMCID: PMC5879439 DOI: 10.1016/j.bone.2018.02.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Revised: 02/19/2018] [Accepted: 02/21/2018] [Indexed: 10/17/2022]
Abstract
PURPOSE Dehydroepiandrosterone (DHEA)+estrogen/progestin therapy for adolescent girls with anorexia nervosa (AN) has the potential to arrest bone loss. The primary aim of this study was to test the effects of DHEA+estrogen/progestin therapy in adolescent girls with AN on bone marrow in the distal femur using magnetic resonance imaging (MRI) and spectroscopy. METHODS Seventy adolescent girls with AN were enrolled in a double blind, randomized, placebo-controlled trial at two urban hospital-based programs. INTERVENTION Seventy-six girls were randomly assigned to receive 12months of either oral micronized DHEA or placebo. DHEA was administered with conjugated equine estrogens (0.3mg daily) for 3months, then an oral contraceptive (20μg ethinyl estradiol/ 0.1mg levonorgestrel) for 9months. The primary outcome measure was bone marrow fat by MRI and magnetic resonance spectroscopy (MRS). RESULTS T2 of the water resonance dropped significantly less in the active vs. placebo group over 12months at both the medial and lateral distal femur (p=0.02). Body mass index (BMI) was a significant effect modifier for T1 and for T2 of unsaturated (T2unsat) and saturated fat (T2sat) in the lateral distal femur. Positive effects of the treatment of DHEA+estrogen/progestin were seen primarily for girls above a BMI of about 18kg/m2. CONCLUSIONS These findings suggest treatment with oral DHEA+estrogen/progestin arrests the age- and disease-related changes in marrow fat composition in the lateral distal femur reported previously in this population.
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Affiliation(s)
- Sridhar Vajapeyam
- Department of Radiology, Boston Children's Hospital, Boston, MA, USA
| | - Kirsten Ecklund
- Department of Radiology, Boston Children's Hospital, Boston, MA, USA
| | - Robert V Mulkern
- Department of Radiology, Boston Children's Hospital, Boston, MA, USA
| | - Henry A Feldman
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, USA
| | | | - Amy D DiVasta
- Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Boston, MA, USA
| | | | - Catherine M Gordon
- Division of Adolescent and Transition Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
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49
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Schoettl T, Fischer IP, Ussar S. Heterogeneity of adipose tissue in development and metabolic function. ACTA ACUST UNITED AC 2018. [PMID: 29514879 DOI: 10.1242/jeb.162958] [Citation(s) in RCA: 131] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Adipose tissue is a central metabolic organ. Unlike other organs, adipose tissue is compartmentalized into individual depots and distributed throughout the body. These different adipose depots show major functional differences and risk associations for developing metabolic syndrome. Recent advances in lineage tracing demonstrate that individual adipose depots are composed of adipocytes that are derived from distinct precursor populations, giving rise to different populations of energy-storing white adipocytes. Moreover, distinct lineages of energy-dissipating brown and beige adipocytes exist in discrete depots or within white adipose tissue depots. In this Review, we discuss developmental and functional heterogeneity, as well as sexual dimorphism, between and within individual adipose tissue depots. We highlight current data relating to the differences between subcutaneous and visceral white adipose tissue in the development of metabolic dysfunction, with special emphasis on adipose tissue expansion and remodeling of the extracellular matrix. Moreover, we provide a detailed overview of adipose tissue development as well as the consensus and controversies relating to adult adipocyte precursor populations.
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Affiliation(s)
- Theresa Schoettl
- JRG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, 85748 Garching, Germany.,German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
| | - Ingrid P Fischer
- JRG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, 85748 Garching, Germany.,German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.,Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany
| | - Siegfried Ussar
- JRG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, 85748 Garching, Germany .,German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
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50
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Ermetici F, Briganti S, Delnevo A, Cannaò P, Leo GD, Benedini S, Terruzzi I, Sardanelli F, Luzi L. Bone marrow fat contributes to insulin sensitivity and adiponectin secretion in premenopausal women. Endocrine 2018. [PMID: 28624865 DOI: 10.1007/s12020-017-1349-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
PURPOSE Bone marrow fat is a functionally distinct adipose tissue that may contribute to systemic metabolism. This study aimed at evaluating a possible association between bone marrow fat and insulin sensitivity indices. METHODS Fifty obese (n = 23) and non-obese (n = 27) premenopausal women underwent proton magnetic resonance spectroscopy to measure vertebral bone marrow fat content and unsaturation index at L4 level. Abdominal visceral, subcutaneous fat, and epicardial fat were also measured using magnetic resonance imaging. Bone mineral density was measured by dual-energy X-ray absorptiometry. Body composition was assessed by bioelectrical impedance analysis. Fasting serum glucose, insulin, lipids, adiponectin were measured; the insulin resistance index HOMA (HOMA-IR) was calculated. RESULTS Bone marrow fat content and unsaturation index were similar in obese and non-obese women (38.5 ± 0.1 vs. 38.6 ± 0.1%, p = 0.994; 0.162 ± 0.065 vs. 0.175 ± 0.048, p = 0.473, respectively). Bone marrow fat content negatively correlated with insulin and HOMA-IR (r = -0.342, r = -0.352, respectively, p = 0.01) and positively with high density lipoprotein cholesterol (r = 0.270, p = 0.043). From a multivariate regression model including lnHOMA-IR as a dependent variable and visceral, subcutaneous, epicardial fat, and bone marrow fat as independent variables, lnHOMA-IR was significantly associated with bone marrow fat (β = -0.008 ± 0.004, p = 0.04) and subcutaneous fat (β = 0.003 ± 0.001, p = 0.04). Bone marrow fat, among the other adipose depots, was a significant predictor of circulating adiponectin (β = 0.147 ± 0.060, p = 0.021). Bone marrow fat unsaturation index negatively correlated with visceral fat (r = -0.316, p = 0.026). CONCLUSIONS There is a relationship between bone marrow fat content and insulin sensitivity in obese and non-obese premenopausal women, possibly mediated by adiponectin secretion. Visceral fat does not seem to regulate bone marrow fat content while it may affect bone marrow fat composition.
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Affiliation(s)
- Federica Ermetici
- Endocrinology and Metabolism, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
| | - Silvia Briganti
- Endocrinology and Metabolism, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Alessandra Delnevo
- Radiology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Paola Cannaò
- Radiology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Giovanni Di Leo
- Radiology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Stefano Benedini
- Endocrinology and Metabolism, IRCCS Policlinico San Donato, San Donato Milanese, Italy
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy
| | - Ileana Terruzzi
- Diabetes Research Institute, Metabolism, Nutrigenomics and Cellular Differentiation Unit, San Raffaele Scientific Institute, Milano, Italy
| | - Francesco Sardanelli
- Radiology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy
| | - Livio Luzi
- Endocrinology and Metabolism, IRCCS Policlinico San Donato, San Donato Milanese, Italy
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy
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