|
1
|
Papavasileiou DA, Leventis M, Agrogiannis G, Kalyvas D. Effect of Isolating the Periosteum With a Resorbable Barrier Membrane on Neoangiogenesis in Guided Bone Regeneration: An Experimental Study. Cureus 2025; 17:e81069. [PMID: 40271309 PMCID: PMC12016391 DOI: 10.7759/cureus.81069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/24/2025] [Indexed: 04/25/2025] Open
Abstract
Introduction In guided bone regeneration, the use of bone substitutes protected by resorbable barrier membranes is suggested for the treatment of bone defects. Sprouting of vessels from surrounding local bone and periosteum into such regenerated areas is an important factor for osteogenesis. However, isolating the grafted area from the overlying periosteum with a barrier membrane may affect the revascularization of the site, thus compromising new bone formation. Aim The aim of this experimental study was to perform a comparative evaluation of neoangiogenesis in bone defects filled with a bone graft and covered with a resorbable barrier membrane or a collagen fleece. Method Eighteen 2.5-3.5 kg weighing New Zealand white rabbits were used. Two circular bicortical bone defects (8 mm in diameter) were created in the calvaria of the animals and subsequently filled with a deproteinized bovine bone mineral ([DBBM]; Bio-Oss®, Geistlich Pharma AG, Wolhusen, Switzerland). One grafted defect was covered with a resorbable collagen membrane (Bio-Guide®, Geistlich Pharma AG) (group A), while the other site was covered by a collagen fleece (Jason® collagen fleece, Botiss Biomaterials GmbH, Zossen, Germany) (group B). The rabbits were divided into three study groups (7, 14, and 28 days), each containing six animals. Specimens were taken, and histological and immunohistological analyses were carried out concerning the number of newly formed vessels. Results All specimens showed uneventful bone formation at 28 days. There was a statistically significant difference in the number of blood vessels for the collagen fleece group at all time periods (7, 14, and 28 days). Conclusions The results of this study indicate that covering a bone graft with a quickly resorbable biomaterial (collagen fleece) allows for a greater degree of neoangiogenesis compared to a resorbable collagen barrier membrane.
Collapse
Affiliation(s)
- Danai Anna Papavasileiou
- Department of Oral and Maxillofacial Surgery, Dental School, National and Kapodistrian University of Athens, Athens, GRC
| | - Minas Leventis
- Department of Oral and Maxillofacial Surgery, Dental School, National and Kapodistrian University of Athens, Athens, GRC
| | - Georgios Agrogiannis
- 1st Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, GRC
| | - Demos Kalyvas
- Department of Oral and Maxillofacial Surgery, Dental School, National and Kapodistrian University of Athens, Athens, GRC
| |
Collapse
|
|
2
|
Li D, Zhang L, Hu T, Ma J, Li X, Zhang X, Kim H. The Cross-Sectional and Longitudinal Associations Between Adherence to 24-Hour Movement Behavior Guidelines and Bone Health in Young Children. Healthcare (Basel) 2024; 12:2173. [PMID: 39517385 PMCID: PMC11544838 DOI: 10.3390/healthcare12212173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 10/28/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Adherence to the World Health Organization's 24-hour movement behavior (24-HMB) guidelines is associated with various health outcomes. However, its relationship with bone mineral density (BMD) in young children has not been investigated. This study aimed to examine the cross-sectional and longitudinal associations between adherence to the 24-HMB guidelines and BMD in young children. METHODS A total of 120 children aged 3-5 years were recruited from three kindergartens in Changsha, Hunan, China. Physical activity (PA) was objectively measured using ActiGraph wGT3X-BT accelerometers, and BMD was assessed using the Sunlight Omnisense 7000P ultrasound device. Screen time (ST) and sleep duration (SD) were reported by parents. Logistic regression was used to analyze the associations between guideline adherence and BMD. RESULTS Only 5.5% of the participants met all three guidelines for PA, ST, and SD, while 16.5% did not meet any. In the cross-sectional analysis, young children who met both ST and SD guidelines (OR = 0.29, 95% CI: 0.09, 0.95) had a lower risk of insufficient BMD compared to those who met none. In the one-year cohort follow-up, young children who met the PA guideline at baseline (OR = 0.22, 95% CI: 0.07, 0.71), as well as those who met both the PA and ST guidelines (OR = 0.18, 95% CI: 0.04, 0.83) or all three (OR = 0.13, 95% CI: 0.03, 0.69), had a lower risk of insufficient BMD at one year. CONCLUSIONS Adherence to the 24-HMB guidelines may promote bone health in young children. Future research should prioritize achievable goals, such as limiting ST and ensuring adequate SD, while gradually increasing MVPA to optimize bone development.
Collapse
Affiliation(s)
- Dan Li
- School of Physical Education, Hunan Normal University, Changsha 410012, China; (D.L.); (T.H.); (X.L.)
| | - Lifang Zhang
- School of Sport Science, Changsha Normal University, Changsha 410100, China;
| | - Ting Hu
- School of Physical Education, Hunan Normal University, Changsha 410012, China; (D.L.); (T.H.); (X.L.)
| | - Jiameng Ma
- Faculty of Sports Science, Sendai University, Shibata 9891693, Japan;
- Physical Education & Sports Science, National Institute of Education, Nanyang Technological University, Singapore 637616, Singapore
| | - Xianxiong Li
- School of Physical Education, Hunan Normal University, Changsha 410012, China; (D.L.); (T.H.); (X.L.)
| | - Xiang Zhang
- School of Physical Education, Hunan Normal University, Changsha 410012, China; (D.L.); (T.H.); (X.L.)
| | - Hyunshik Kim
- Faculty of Sports Science, Sendai University, Shibata 9891693, Japan;
- Physical Education & Sports Science, National Institute of Education, Nanyang Technological University, Singapore 637616, Singapore
| |
Collapse
|
|
3
|
Bojtor B, Balla B, Vaszilko M, Szentpeteri S, Putz Z, Kosa JP, Lakatos P. Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives. Int J Mol Sci 2024; 25:10488. [PMID: 39408816 PMCID: PMC11477157 DOI: 10.3390/ijms251910488] [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] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/19/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction.
Collapse
Affiliation(s)
- Bence Bojtor
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
| | - Bernadett Balla
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
| | - Mihaly Vaszilko
- Department of Oro-Maxillofacial Surgery and Stomatology, Semmelweis University, 1085 Budapest, Hungary; (M.V.); (S.S.)
| | - Szofia Szentpeteri
- Department of Oro-Maxillofacial Surgery and Stomatology, Semmelweis University, 1085 Budapest, Hungary; (M.V.); (S.S.)
| | - Zsuzsanna Putz
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
| | - Janos P. Kosa
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
| | - Peter Lakatos
- Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (B.B.); (Z.P.); (J.P.K.)
- Hungarian Research Network SE-ENDOMOLPAT Research Group, 1085 Budapest, Hungary;
| |
Collapse
|
|
4
|
Zhou XC, Wang DX, Zhang CY, Yang YJ, Zhao RB, Liu SY, Ni GX. Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis. World J Orthop 2024; 15:363-378. [PMID: 38680671 PMCID: PMC11045468 DOI: 10.5312/wjo.v15.i4.363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 02/04/2024] [Accepted: 03/19/2024] [Indexed: 04/16/2024] Open
Abstract
BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation. AIM To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms. METHODS 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation. RESULTS Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence. CONCLUSION Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.
Collapse
Affiliation(s)
- Xu-Chang Zhou
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Dong-Xue Wang
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Chun-Yu Zhang
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Ya-Jing Yang
- Department of Acupuncture and Moxibustion, Hubei University of Chinese Medicine, Wuhan 430065, Hubei Province, China
| | - Ruo-Bing Zhao
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Sheng-Yao Liu
- Department of Spinal Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Guo-Xin Ni
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian Province, China
| |
Collapse
|
|
5
|
Wazzani R, Bourzac C, Elhafci H, Germain P, Ahmaidi S, Pallu S, Jaffré C, Portier H. Comparative effects of various running exercise modalities on femoral bone quality in rats. Eur J Appl Physiol 2024; 124:761-773. [PMID: 37690048 DOI: 10.1007/s00421-023-05293-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 07/31/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND It is now well established that physical exercise is an effective preventive method to reduce and treat certain chronic diseases, particularly musculoskeletal disorders. At the bone level, running exercise is well known for its positive effects on various parameters of bone quality. There is, however, no consensus regarding the effects of different running exercise modalities on bone quality. AIM The objective of this study was to compare the effects of three treadmill running modalities: intermittent, moderate continuous, and a combination of both-on bone quality parameters in rats. METHODS Thirty-nine, 5-week-old, male Wistar rats were randomly divided in 4 groups: sedentary control (SED; n = 10), intermittent running exercise (IE; n = 10), continuous running exercise (CE; n = 10) and combined running exercise (COME; n = 9). Rats in running groups were exercised 45 min/day, 5 days/week, for 8 consecutive weeks. Femoral micro-architectural parameters were assessed by micro-CT; femoral osteocyte apoptosis, osteoclast resorption and bone histomorphometry were assessed by histology. RESULTS Femoral trabecular thickness in the combined running group was increased (p < 0.0001) compared to respective results in the other running groups (0.13 mm vs 0.11 mm). The cortical thickness, osteocyte lacunae occupancy rate in the whole femur, numbers of apoptotic osteocytes and osteoclastic resorption surfaces were not significantly different between groups. Statistical differences were occasionally noted depending on the femoral anatomical region. CONCLUSION These results suggest that the femur should not be considered as the better bone to study the effects of running protocols.
Collapse
Affiliation(s)
- Rkia Wazzani
- Laboratory APERE, University de Picardie Jules Verne, Avenue Paul Claudel, 80000, Amiens, France
| | - Céline Bourzac
- B3OA Laboratory, CNRS 7052, INSERM 1271, University of Paris, 10 Avenue de Verdun, 75010, Paris, France
- Plateforme de recherche biomédicale, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France
| | - Hanane Elhafci
- B3OA Laboratory, CNRS 7052, INSERM 1271, University of Paris, 10 Avenue de Verdun, 75010, Paris, France
| | - Philippe Germain
- Research Group Sport, Physical Activity, Rehabilitation and Movement for Performance and Health, University of Orleans, 45067, Orléans, France
- Centre de Biophysique Moléculaire (CBM), UPR CNRS 4301, Université d'Orléans, Rue Charles Sandron, CS 80054, 45071, Orléans, France
| | - Said Ahmaidi
- Laboratory APERE, University de Picardie Jules Verne, Avenue Paul Claudel, 80000, Amiens, France
| | - Stéphane Pallu
- B3OA Laboratory, CNRS 7052, INSERM 1271, University of Paris, 10 Avenue de Verdun, 75010, Paris, France
- Research Group Sport, Physical Activity, Rehabilitation and Movement for Performance and Health, University of Orleans, 45067, Orléans, France
| | - Christelle Jaffré
- Laboratory APERE, University de Picardie Jules Verne, Avenue Paul Claudel, 80000, Amiens, France
| | - Hugues Portier
- B3OA Laboratory, CNRS 7052, INSERM 1271, University of Paris, 10 Avenue de Verdun, 75010, Paris, France.
- Research Group Sport, Physical Activity, Rehabilitation and Movement for Performance and Health, University of Orleans, 45067, Orléans, France.
| |
Collapse
|
|
6
|
Tang L, Guo H, Wang K, Zhou Y, Wu T, Fan X, Guo J, Sun L, Ta D. Low-intensity pulsed ultrasound enhances the positive effects of high-intensity treadmill exercise on bone in rats. J Bone Miner Metab 2023; 41:592-605. [PMID: 37270713 DOI: 10.1007/s00774-023-01439-6] [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: 11/10/2022] [Accepted: 05/09/2023] [Indexed: 06/05/2023]
Abstract
INTRODUCTION Moderate exercise benefits bone health, but excessive loading leads to bone fatigue and a decline in mechanical properties. Low-intensity pulsed ultrasound (LIPUS) can stimulate bone formation. The purpose of this study was to explore whether LIPUS could augment the skeletal benefits of high-intensity exercise. MATERIALS AND METHODS MC3T3-E1 osteoblasts were treated with LIPUS at 80 mW/cm2 or 30 mW/cm2 for 20 min/day. Forty rats were divided into sham treatment normal control (Sham-NC), sham treatment high-intensity exercise (Sham-HIE), 80 mW/cm2 LIPUS (LIPUS80), and high-intensity exercise combined with 80 mW/cm2 LIPUS (LIPUS80-HIE). The rats in HIE group were subjected to 30 m/min slope treadmill exercise for 90 min/day, 6 days/week for 12 weeks. The LIPUS80-HIE rats were irradiated with LIPUS (1 MHz, 80 mW/cm2) for 20 min/day at bilateral hind limb after exercise. RESULTS LIPUS significantly accelerated the proliferation, differentiation, mineralization, and migration of MC3T3-E1 cells. Compared to 30 mW/cm2 LIPUS, 80 mW/cm2 LIPUS got better promotion effect. 12 weeks of high-intensity exercise significantly reduced the muscle force, which was significantly reversed by LIPUS. Compared with the Sham-NC group, Sham-HIE group significantly optimized bone microstructure and enhanced mechanical properties of femur, and LIPUS80-HIE further enhanced the improvement effect on bone. The mechanisms may be related to activate Wnt/β-catenin signal pathway and then up-regulate the protein expression of Runx2 and VEGF, the key factors of osteogenesis and angiogenesis. CONCLUSION LIPUS could augment the skeletal benefits of high-intensity exercise through Wnt/β-catenin signal pathway.
Collapse
Affiliation(s)
- Liang Tang
- Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China
| | - Hao Guo
- Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China
- School of Physical Education, Bohai University, Jinzhou, 121013, China
| | - Keyi Wang
- Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China
| | - Yaling Zhou
- Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China
| | - Tianpei Wu
- Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China
| | - Xiushan Fan
- Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China
| | - Jianzhong Guo
- Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University, Xi'an, 710119, China
| | - Lijun Sun
- Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China.
| | - Dean Ta
- Department of Electronic Engineering, Fudan University, Shanghai, 200433, China.
- Academy for Engineering and Technology, Fudan University, Shanghai, 201203, China.
| |
Collapse
|
|
7
|
Suntornsaratoon P, Thongklam T, Saetae T, Kodmit B, Lapmanee S, Malaivijitnond S, Charoenphandhu N, Krishnamra N. Running exercise with and without calcium supplementation from tuna bone reduced bone impairment caused by low calcium intake in young adult rats. Sci Rep 2023; 13:9568. [PMID: 37311761 DOI: 10.1038/s41598-023-36561-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 06/06/2023] [Indexed: 06/15/2023] Open
Abstract
Inadequate calcium intake during childhood and adolescence is detrimental to bone metabolism. Here, we postulated that calcium supplement prepared from tuna bone with tuna head oil should benefit for skeletal development than CaCO3. Forty female 4-week-old rats were divided into calcium-replete diet (0.55% w/w, S1, n = 8) and low-calcium groups (0.15% w/w for 2 weeks; L; n = 32). Then L were subdivided into 4 groups (8/group), i.e., remained on L, L + tuna bone (S2), S2 + tuna head oil + 25(OH)D3 and S2 + 25(OH)D3. Bone specimens were collected at week 9. We found that 2 weeks on low calcium diet led to low bone mineral density (BMD), reduced mineral content, and impaired mechanical properties in young growing rats. Intestinal fractional calcium absorption also increased, presumably resulting from higher plasma 1,25(OH)2D3 (1.712 ± 0.158 in L vs. 1.214 ± 0.105 nM in S1, P < 0.05). Four-week calcium supplementation from tuna bone further increased calcium absorption efficacy, which later returned to the basal level by week 9. Calcium supplementation successfully restored BMD, bone strength and microstructure. However, 25(OH)D3 + tuna head oil + tuna bone showed no additive effect. Voluntary running also effectively prevented bone defects. In conclusion, both tuna bone calcium supplementation and exercise are effective interventions for mitigating calcium-deficient bone loss.
Collapse
Affiliation(s)
- Panan Suntornsaratoon
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
- Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand.
| | - Thachakorn Thongklam
- Global Innovation Center, Thai Union Group Public Company Limited, Bangkok, Thailand
| | - Thaweechai Saetae
- Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
| | - Buapuengporn Kodmit
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
- Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Sarawut Lapmanee
- Department of Basic Medical Sciences, Faculty of Medicine, Siam University, Bangkok, Thailand
| | - Suchinda Malaivijitnond
- Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
- National Primate Research Center of Thailand, Chulalongkorn University, Saraburi, Thailand
| | - Narattaphol Charoenphandhu
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
- Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand
- Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
- The Academy of Science, The Royal Society of Thailand, Dusit, Bangkok, Thailand
| | - Nateetip Krishnamra
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
- Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand
| |
Collapse
|
|
8
|
Vande Berg BC, Mourad C, Omoumi P, Malghem J. Magnetic Resonance Imaging of Accelerated Bone Remodeling. Semin Musculoskelet Radiol 2023; 27:114-123. [PMID: 36868249 DOI: 10.1055/s-0043-1761611] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023]
Abstract
A regional acceleration of bone remodeling may possibly follow biomechanical insults to the bone. This review assesses the literature and clinical arguments supporting the hypothetical association between accelerated bone remodeling and bone marrow edema (BME)-like signal intensity on magnetic resonance imaging. BME-like signal is defined as a confluent ill-delimited area of bone marrow with a moderate decrease in signal intensity on fat-sensitive sequences and a high signal intensity on fat-suppressed fluid-sensitive sequences. In addition to this confluent pattern, a linear subcortical pattern and a patchy disseminated pattern have also been recognized on fat-suppressed fluid-sensitive sequences. These particular BME-like patterns may remain occult on T1-weighted spin-echo images. We hypothesize that these BME-like patterns, with particular characteristics in terms of distribution and signal, are associated with accelerated bone remodeling. Limitations in recognizing these BME-like patterns are also discussed.
Collapse
Affiliation(s)
- Bruno C Vande Berg
- Department of Radiology, Musculoskeletal Section, Centre Hospitalier Chrétien, CHC, Clinique Mont Legia, Liege, Belgium
| | - Charbel Mourad
- Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.,Department of Diagnostic and Interventional Radiology, Hôpital Libanais Geitaoui- CHU, Beyrouth, Lebanon
| | - Patrick Omoumi
- Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Jacques Malghem
- Department of Radiology, Cliniques Universitaires Saint-Luc Université Catholique de Louvain, Brussels, Belgium
| |
Collapse
|
|
9
|
Molecular mechanisms of exercise contributing to tissue regeneration. Signal Transduct Target Ther 2022; 7:383. [PMID: 36446784 PMCID: PMC9709153 DOI: 10.1038/s41392-022-01233-2] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 10/03/2022] [Accepted: 10/17/2022] [Indexed: 12/03/2022] Open
Abstract
Physical activity has been known as an essential element to promote human health for centuries. Thus, exercise intervention is encouraged to battle against sedentary lifestyle. Recent rapid advances in molecular biotechnology have demonstrated that both endurance and resistance exercise training, two traditional types of exercise, trigger a series of physiological responses, unraveling the mechanisms of exercise regulating on the human body. Therefore, exercise has been expected as a candidate approach of alleviating a wide range of diseases, such as metabolic diseases, neurodegenerative disorders, tumors, and cardiovascular diseases. In particular, the capacity of exercise to promote tissue regeneration has attracted the attention of many researchers in recent decades. Since most adult human organs have a weak regenerative capacity, it is currently a key challenge in regenerative medicine to improve the efficiency of tissue regeneration. As research progresses, exercise-induced tissue regeneration seems to provide a novel approach for fighting against injury or senescence, establishing strong theoretical basis for more and more "exercise mimetics." These drugs are acting as the pharmaceutical alternatives of those individuals who cannot experience the benefits of exercise. Here, we comprehensively provide a description of the benefits of exercise on tissue regeneration in diverse organs, mainly focusing on musculoskeletal system, cardiovascular system, and nervous system. We also discuss the underlying molecular mechanisms associated with the regenerative effects of exercise and emerging therapeutic exercise mimetics for regeneration, as well as the associated opportunities and challenges. We aim to describe an integrated perspective on the current advances of distinct physiological mechanisms associated with exercise-induced tissue regeneration on various organs and facilitate the development of drugs that mimics the benefits of exercise.
Collapse
|
|
10
|
Zmudzka M, Zoladz JA, Majerczak J. The impact of aging and physical training on angiogenesis in the musculoskeletal system. PeerJ 2022; 10:e14228. [PMID: 36348663 PMCID: PMC9637352 DOI: 10.7717/peerj.14228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 09/22/2022] [Indexed: 11/06/2022] Open
Abstract
Angiogenesis is the physiological process of capillary growth. It is strictly regulated by the balanced activity of agents that promote the formation of capillaries (pro-angiogenic factors) on the one hand and inhibit their growth on the other hand (anti-angiogenic factors). Capillary rarefaction and insufficient angiogenesis are some of the main causes that limit blood flow during aging, whereas physical training is a potent non-pharmacological method to intensify capillary growth in the musculoskeletal system. The main purpose of this study is to present the current state of knowledge concerning the key signalling molecules implicated in the regulation of skeletal muscle and bone angiogenesis during aging and physical training.
Collapse
Affiliation(s)
- Magdalena Zmudzka
- Chair of Exercise Physiology and Muscle Bioenergetics, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland
| | - Jerzy A. Zoladz
- Chair of Exercise Physiology and Muscle Bioenergetics, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland
| | - Joanna Majerczak
- Chair of Exercise Physiology and Muscle Bioenergetics, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland
| |
Collapse
|
|
11
|
Effects of Exercise or Mechanical Stimulation on Bone Development and Bone Repair. Stem Cells Int 2022; 2022:5372229. [PMID: 36213684 PMCID: PMC9534715 DOI: 10.1155/2022/5372229] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/07/2022] [Indexed: 11/25/2022] Open
Abstract
The development and regeneration of the bone are tightly regulated by mechanical cues. Multiple cell types, including osteoblasts, osteocytes, osteoclasts, mesenchymal stem cells (MSCs), and recently found skeletal stem cells (SSCs), are responsible for efficient bone development and injury repair. The immune cells in the environment interact with bone cells to maintain homeostasis and facilitate bone regeneration. Investigation of the mechanism by which these cells sense and respond to mechanical signals in bone is fundamental for optimal clinical intervention in bone injury healing. We discuss the effects of exercise programs on fracture healing in animal models and human patients, which encouragingly suggest that carefully designed exercise prescriptions can improve the result of fracture healing during the remodeling phase. However, additional clinical tracing and date accumulation are still required for the pervasive application of exercise prescriptions to improve fracture healing.
Collapse
|
|
12
|
Sun X, Li K, Li BY, Yokota H. Wnt signaling: a double-edged sword in protecting bone from cancer. J Bone Miner Metab 2022; 41:365-370. [PMID: 36040520 DOI: 10.1007/s00774-022-01363-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/29/2022] [Indexed: 11/30/2022]
Abstract
Wnt signaling plays a critical role in loading-driven bone formation and bone homeostasis, whereas its activation in cancer cells promotes their progression. Currently, major research efforts in cancer treatment have been directed to the development of Wnt inhibitors. Recent studies on tumor-bone interactions, however, presented multiple lines of evidence that support a tumor-suppressive role of Lrp5, a Wnt co-receptor, and β-catenin, in Wnt signaling. This review describes the action of Wnt signaling as a double-edged sword in the bone microenvironment and suggests the possibility of a novel option for protecting bone from cancer.
Collapse
Affiliation(s)
- Xun Sun
- Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, 150081, China
- Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, 723 West Michigan Street, SL220, Indianapolis, IN, 46202, USA
| | - Kexin Li
- Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, 150081, China
- Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, 723 West Michigan Street, SL220, Indianapolis, IN, 46202, USA
| | - Bai-Yan Li
- Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, 150081, China
| | - Hiroki Yokota
- Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, 723 West Michigan Street, SL220, Indianapolis, IN, 46202, USA.
- Simon Comprehensive Cancer Center, Indianapolis, IN, 46202, USA.
- Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
| |
Collapse
|
|
13
|
Ju YI, Sone T. Effects of Different Types of Mechanical Loading on Trabecular Bone Microarchitecture in Rats. J Bone Metab 2021; 28:253-265. [PMID: 34905673 PMCID: PMC8671029 DOI: 10.11005/jbm.2021.28.4.253] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 10/06/2021] [Indexed: 11/21/2022] Open
Abstract
Mechanical loading is generally considered to have a positive impact on the skeleton; however, not all types of mechanical loading have the same beneficial effect. Many researchers have investigated which types of mechanical loading are more effective for improving bone mass and strength. Among the various mechanical loads, high-impact loading, such as jumping, appears to be more beneficial for bones than low-impact loadings such as walking, running, or swimming. Therefore, the different forms of mechanical loading exerted by running, swimming, and jumping exercises may have different effects on bone adaptations. However, little is known about the relationships between the types of mechanical loading and their effects on trabecular bone structure. The purpose of this article is to review the recent reports on the effects of treadmill running, jumping, and swimming on the trabecular bone microarchitecture in small animals. The effects of loading on trabecular bone architecture appear to differ among these different exercises, as several reports have shown that jumping increases the trabecular bone mass by thickening the trabeculae, whereas treadmill running and swimming add to the trabecular bone mass by increasing the trabecular number, rather than the thickness. This suggests that different types of exercise promote gains in trabecular bone mass through different architectural patterns in small animals.
Collapse
Affiliation(s)
- Yong-In Ju
- Department of Health and Sports Sciences, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan
| | - Teruki Sone
- Department of Nuclear Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan
| |
Collapse
|
|
14
|
Wazzani R, Pallu S, Bourzac C, Ahmaïdi S, Portier H, Jaffré C. Physical Activity and Bone Vascularization: A Way to Explore in Bone Repair Context? Life (Basel) 2021; 11:life11080783. [PMID: 34440527 PMCID: PMC8399402 DOI: 10.3390/life11080783] [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: 03/17/2021] [Revised: 06/11/2021] [Accepted: 07/21/2021] [Indexed: 01/15/2023] Open
Abstract
Physical activity is widely recognized as a biotherapy by WHO in the fight and prevention of bone diseases such as osteoporosis. It reduces the risk of disabling fractures associated with many comorbidities, and whose repair is a major public health and economic issue. Bone tissue is a dynamic supportive tissue that reshapes itself according to the mechanical stresses to which it is exposed. Physical exercise is recognized as a key factor for bone health. However, the effects of exercise on bone quality depend on exercise protocols, duration, intensity, and frequency. Today, the effects of different exercise modalities on capillary bone vascularization, bone blood flow, and bone angiogenesis remain poorly understood and unclear. As vascularization is an integral part of bone repair process, the analysis of the preventive and/or curative effects of physical exercise is currently very undeveloped. Angiogenesis–osteogenesis coupling may constitute a new way for understanding the role of physical activity, especially in fracturing or in the integration of bone biomaterials. Thus, this review aimed to clarify the link between physical activities, vascularization, and bone repair.
Collapse
Affiliation(s)
- Rkia Wazzani
- Laboratoire APERE, Université de Picardie Jules Verne, CEDEX, F-80000 Amiens, France; (R.W.); (S.A.)
| | - Stéphane Pallu
- Laboratoire B3OA, Université de Paris, CEDEX, F-75010 Paris, France; (S.P.); (C.B.); (H.P.)
- UFR Science & Technique, Université d’Orléans, CEDEX, F-45100 Orléans, France
| | - Céline Bourzac
- Laboratoire B3OA, Université de Paris, CEDEX, F-75010 Paris, France; (S.P.); (C.B.); (H.P.)
| | - Saïd Ahmaïdi
- Laboratoire APERE, Université de Picardie Jules Verne, CEDEX, F-80000 Amiens, France; (R.W.); (S.A.)
| | - Hugues Portier
- Laboratoire B3OA, Université de Paris, CEDEX, F-75010 Paris, France; (S.P.); (C.B.); (H.P.)
- UFR Science & Technique, Université d’Orléans, CEDEX, F-45100 Orléans, France
| | - Christelle Jaffré
- Laboratoire APERE, Université de Picardie Jules Verne, CEDEX, F-80000 Amiens, France; (R.W.); (S.A.)
- Laboratoire B3OA, Université de Paris, CEDEX, F-75010 Paris, France; (S.P.); (C.B.); (H.P.)
- Correspondence:
| |
Collapse
|
|
15
|
Loss of Wnt16 Leads to Skeletal Deformities and Downregulation of Bone Developmental Pathway in Zebrafish. Int J Mol Sci 2021; 22:ijms22136673. [PMID: 34206401 PMCID: PMC8268848 DOI: 10.3390/ijms22136673] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/16/2021] [Accepted: 06/18/2021] [Indexed: 12/21/2022] Open
Abstract
Wingless-type MMTV integration site family, member 16 (wnt16), is a wnt ligand that participates in the regulation of vertebrate skeletal development. Studies have shown that wnt16 can regulate bone metabolism, but its molecular mechanism remains largely undefined. We obtained the wnt16−/− zebrafish model using the CRISPR-Cas9-mediated gene knockout screen with 11 bp deletion in wnt16, which led to the premature termination of amino acid translation and significantly reduced wnt16 expression, thus obtaining the wnt16−/− zebrafish model. The expression of wnt16 in bone-related parts was detected via in situ hybridization. The head, spine, and tail exhibited significant deformities, and the bone mineral density and trabecular bone decreased in wnt16−/− using light microscopy and micro-CT analysis. RNA sequencing was performed to explore the differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the down-regulated DEGs are mainly concentrated in mTOR, FoxO, and VEGF pathways. Protein–protein interaction (PPI) network analysis was performed with the detected DEGs. Eight down-regulated DEGs including akt1, bnip4, ptena, vegfaa, twsg1b, prkab1a, prkab1b, and pla2g4f.2 were validated by qRT-PCR and the results were consistent with the RNA-seq data. Overall, our work provides key insights into the influence of wnt16 gene on skeletal development.
Collapse
|
|
16
|
de Lamas C, Sánchez-Pintos P, José de Castro M, Sáenz de Pipaon M, Couce ML. Screen Time and Bone Status in Children and Adolescents: A Systematic Review. Front Pediatr 2021; 9:675214. [PMID: 34926335 PMCID: PMC8672244 DOI: 10.3389/fped.2021.675214] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 11/11/2021] [Indexed: 12/18/2022] Open
Abstract
Introduction: Technological advances over the last 2 decades have led to an increase in the time spent by children and youth engaged in screen-based activities, and growing recognition of deleterious effects on health. In this systematic review of cohort and cross-sectional studies, we assess current data on the relationship between screen time and bone status in children and teenagers. Methods: We searched PUBMED and SCOPUS databases for studies of children and adolescents that assessed screen time and bone status, determined by measuring bone mineral content or density, bone stiffness index, bone speed of sound, bone broadband ultrasound attenuation, or frame index. Searches were limited to studies published between 1900 and 2020, and performed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The studies included were evaluated using the Newcastle-Ottawa quality assessment scale. Results: Ten cohort and cross-sectional studies including pediatric population were selected. The combined study population was 20,420 children/adolescents, of whom 18,444 participated in cross-sectional studies. Four studies assessed the effects of total screen time, seven the consequences of TV viewing time, and six the effects of recreational computer use on bone health. Our findings indicate an inverse association between total and weekly screen time and bone health in children and adolescents. In 57% of the studies included also a negative correlation between television viewing time and bone status was observed, while recreational computer time did not have a significant impact on bone health. According to the only four studies that included dietetic factors, no relevant differences were found between calcium intake and screen time or bone broadband ultrasound attenuation and bone speed of sound. Conclusions: Review of the literature of the past three decades provides strong support for comprehensive education of screen time on bone status. The findings of this systematic review support a negative association between screen time and bone status in children and adolescents, with a different impact when considering the different technological devices. As peak bone mass in adolescents is the strongest predictor of osteoporosis risk, strategies aimed at improving bone health should incorporate conscious use of digital technology.
Collapse
Affiliation(s)
- Carmela de Lamas
- Santiago de Compostela University, Santiago de Compostela, Spain
| | - Paula Sánchez-Pintos
- Santiago de Compostela University, Santiago de Compostela, Spain.,Metabolic Unit, Neonatology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.,European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), Madrid, Spain.,Rare Diseases Networking Biomedical Research Centre (CIBERER), Madrid, Spain
| | - María José de Castro
- Santiago de Compostela University, Santiago de Compostela, Spain.,Metabolic Unit, Neonatology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.,European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), Madrid, Spain.,Rare Diseases Networking Biomedical Research Centre (CIBERER), Madrid, Spain
| | - Miguel Sáenz de Pipaon
- Department of Pediatrics-Neonatology, Autonomous University of Madrid, La Paz University Hospital, Madrid, Spain
| | - María Luz Couce
- Santiago de Compostela University, Santiago de Compostela, Spain.,Metabolic Unit, Neonatology Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.,European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), Madrid, Spain.,Rare Diseases Networking Biomedical Research Centre (CIBERER), Madrid, Spain
| |
Collapse
|
|
17
|
Portier H, Benaitreau D, Pallu S. Does Physical Exercise Always Improve Bone Quality in Rats? Life (Basel) 2020; 10:life10100217. [PMID: 32977460 PMCID: PMC7598192 DOI: 10.3390/life10100217] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 12/17/2022] Open
Abstract
For decades, the osteogenic effect from different physical activities on bone in rodents remained uncertain. This literature review presents for the first time the effects on five exercise models (treadmill running, wheel running, swimming, resistance training and vibration modes) in three different experimental rat groups (males, females, osteopenic) on bone quality. The bone parameters presented are bone mineral density, micro-architectural and mechanical properties, and osteoblast/osteocyte and osteoclast parameters. This review shows that physical activities have a positive effect (65% of the results) on bone status, but we clearly observed a difference amongst the different protocols. Even if treadmill running is the most used protocol, the resistance training constitutes the first exercise model in term of osteogenic effects (87% of the whole results obtained on this model). The less osteogenic model is the vibration mode procedure (31%). It clearly appears that the gender plays a role on the bone response to swimming and wheel running exercises. Besides, we did not observe negative results in the osteopenic population with impact training, wheel running and vibration activities. Moreover, about osteoblast/osteocyte parameters, we conclude that high impact and resistance exercise (such jumps and tower climbing) seems to increase bone formation more than running or aerobic exercise. Among the different protocols, literature has shown that the treadmill running procedure mainly induces osteogenic effects on the viability of the osteocyte lineage in both males and females or ovariectomized rats; running in voluntary wheels contributes to a negative effect on bone metabolism in older male models; whole-body vertical vibration is not an osteogenic exercise in female and ovariectomized rats; whereas swimming provides controversial results in female models. For osteoclast parameters only, running in a voluntary wheel for old males, the treadmill running program at high intensity in ovariectomized rats, and the swimming program in a specific ovariectomy condition have detrimental consequences.
Collapse
Affiliation(s)
- Hugues Portier
- Laboratoire de Biologie Bioingénierie et Bioimagerie Ostéo-Articulaire (B3OA), Université Paris, UMR CNRS 7052, INSERM U1273, 10 Av de Verdun, 75010 Paris, France;
- Collegium Science & Technique, 2 allée du château, Université d’Orléans. 45100 Orléans, France;
- Correspondence: ; Tel.: +33-782-309-433
| | - Delphine Benaitreau
- Collegium Science & Technique, 2 allée du château, Université d’Orléans. 45100 Orléans, France;
| | - Stéphane Pallu
- Laboratoire de Biologie Bioingénierie et Bioimagerie Ostéo-Articulaire (B3OA), Université Paris, UMR CNRS 7052, INSERM U1273, 10 Av de Verdun, 75010 Paris, France;
- Collegium Science & Technique, 2 allée du château, Université d’Orléans. 45100 Orléans, France;
| |
Collapse
|
|
18
|
Margaritelis NV, Paschalis V, Theodorou AA, Kyparos A, Nikolaidis MG. Redox basis of exercise physiology. Redox Biol 2020; 35:101499. [PMID: 32192916 PMCID: PMC7284946 DOI: 10.1016/j.redox.2020.101499] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 02/20/2020] [Accepted: 03/05/2020] [Indexed: 12/15/2022] Open
Abstract
Redox reactions control fundamental processes of human biology. Therefore, it is safe to assume that the responses and adaptations to exercise are, at least in part, mediated by redox reactions. In this review, we are trying to show that redox reactions are the basis of exercise physiology by outlining the redox signaling pathways that regulate four characteristic acute exercise-induced responses (muscle contractile function, glucose uptake, blood flow and bioenergetics) and four chronic exercise-induced adaptations (mitochondrial biogenesis, muscle hypertrophy, angiogenesis and redox homeostasis). Based on our analysis, we argue that redox regulation should be acknowledged as central to exercise physiology.
Collapse
Affiliation(s)
- N V Margaritelis
- Department of Physical Education and Sport Science at Serres, Aristotle University of Thessaloniki, Thessaloniki, Greece; Dialysis Unit, 424 General Military Hospital of Thessaloniki, Thessaloniki, Greece.
| | - V Paschalis
- School of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece
| | - A A Theodorou
- Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus
| | - A Kyparos
- Department of Physical Education and Sport Science at Serres, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - M G Nikolaidis
- Department of Physical Education and Sport Science at Serres, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| |
Collapse
|
|
19
|
Abstract
The skeleton is highly vascularized due to the various roles blood vessels play in the homeostasis of bone and marrow. For example, blood vessels provide nutrients, remove metabolic by-products, deliver systemic hormones, and circulate precursor cells to bone and marrow. In addition to these roles, bone blood vessels participate in a variety of other functions. This article provides an overview of the afferent, exchange and efferent vessels in bone and marrow and presents the morphological layout of these blood vessels regarding blood flow dynamics. In addition, this article discusses how bone blood vessels participate in bone development, maintenance, and repair. Further, mechanical loading-induced bone adaptation is presented regarding interstitial fluid flow and pressure, as regulated by the vascular system. The role of the sympathetic nervous system is discussed in relation to blood vessels and bone. Finally, vascular participation in bone accrual with intermittent parathyroid hormone administration, a medication prescribed to combat age-related bone loss, is described and age- and disease-related impairments in blood vessels are discussed in relation to bone and marrow dysfunction. © 2020 American Physiological Society. Compr Physiol 10:1009-1046, 2020.
Collapse
Affiliation(s)
- Rhonda D Prisby
- Bone Vascular and Microcirculation Laboratory, Department of Kinesiology, University of Texas at Arlington, Arlington, Texas, USA
| |
Collapse
|
|
20
|
Fenelon M, Etchebarne M, Siadous R, Grémare A, Durand M, Sentilhes L, Torres Y, Catros S, Gindraux F, L'Heureux N, Fricain JC. Assessment of fresh and preserved amniotic membrane for guided bone regeneration in mice. J Biomed Mater Res A 2020; 108:2044-2056. [PMID: 32319212 DOI: 10.1002/jbm.a.36964] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 03/23/2020] [Accepted: 03/28/2020] [Indexed: 12/13/2022]
Abstract
Thanks to its biological properties, the human amniotic membrane (HAM) can be used as a barrier membrane for guided bone regeneration (GBR). However, no study has assessed the influence of the preservation method of HAM for this application. This study aimed to establish the most suitable preservation method of HAM for GBR. Fresh (F), cryopreserved (C) lyophilized (L), and decellularized and lyophilized (DL) HAM were compared. The impact of preservation methods on collagen and glycosaminoglycans (GAG) content was evaluated using Masson's trichrome and alcian blue staining. Their suture retention strengths were assessed. In vitro, the osteogenic potential of human bone marrow mesenchymal stromal cells (hBMSCs) cultured on the four HAMs was evaluated using alkaline phosphatase staining and alizarin red quantification assay. In vivo, the effectiveness of fresh and preserved HAMs for GBR was assessed in a mice diaphyseal bone defect after 1 week or 1 month healing. Micro-CT and histomorphometric analysis were performed. The major structural components of HAM (collagen and GAG) were preserved whatever the preservation method used. The tearing strength of DL-HAM was significantly higher. In vitro, hBMSCs seeded on DL-HAM displayed a stronger ALP staining, and alizarin red staining quantification was significantly higher at Day 14. In vivo, L-HAM and DL-HAM significantly enhanced early bone regeneration. One month after the surgery, only DL-HAM slightly promoted bone regeneration. Several preserving methods of HAM have been studied for bone regeneration. Here, we have demonstrated that DL-HAM achieved the most promising results for GBR.
Collapse
Affiliation(s)
- Mathilde Fenelon
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France.,Department of Oral Surgery, CHU Bordeaux, Bordeaux, France
| | - Marion Etchebarne
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France.,Department of Maxillofacial Surgery, CHU Bordeaux, Bordeaux, France
| | - Robin Siadous
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France
| | - Agathe Grémare
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France.,Department of Odontology and Oral Health, CHU Bordeaux, Bordeaux, France
| | - Marlène Durand
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France.,CHU Bordeaux, CIC 1401, Bordeaux, France.,INSERM, CIC 1401, Bordeaux, France
| | - Loic Sentilhes
- Department of Obstetrics and Gynecology, Bordeaux University Hospital, University of Bordeaux, Bordeaux, France
| | - Yoann Torres
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France
| | - Sylvain Catros
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France.,Department of Oral Surgery, CHU Bordeaux, Bordeaux, France
| | - Florelle Gindraux
- Department of Orthopedic, Traumatology & Plastic Surgery, University Hospital of Besançon, Besançon, France.,Nanomedicine Lab, Imagery and Therapeutics (EA 4662), SFR FED 4234, University of Franche-Comté, Besançon, France
| | - Nicolas L'Heureux
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France
| | - Jean-Christophe Fricain
- INSERM, Laboratory BioTis, UMR 1026, University of Bordeaux, Bordeaux, France.,Department of Oral Surgery, CHU Bordeaux, Bordeaux, France
| |
Collapse
|
|
21
|
Lee S, Prisby RD. Short-term intermittent parathyroid hormone (1-34) administration increased angiogenesis and matrix metalloproteinase 9 in femora of mature and middle-aged C57BL/6 mice. Exp Physiol 2020; 105:1159-1171. [PMID: 32306445 DOI: 10.1113/ep087869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 04/15/2020] [Indexed: 01/09/2023]
Abstract
NEW FINDINGS What is the central question of this study? We sought to assess the effects of intermittent parathyroid hormone (1-34) administration on bone angiogenesis, the redistribution of bone marrow blood vessels, and matrix metalloproteinase 9 as a function of advancing age in mice. What is the main finding and its importance? Short-term (i.e. 10 days) intermittent parathyroid hormone (1-34) administration increased the number of small (≤29-µm-diameter) bone marrow blood vessels and augmented matrix metalloproteinase 9. These changes occurred before alterations in trabecular bone. Given the rapid response in bone angiogenesis, this investigation highlights the impact of intermittent parathyroid hormone (1-34) administration on the bone vascular network. ABSTRACT Intermittent parathyroid hormone (PTH) administration augments bone, stimulates the production of matrix metalloproteinase 9 (Mmp9) and relocates bone marrow blood vessels closer to osteoid seams. Discrepancies exist, however, regarding bone angiogenesis. Given that Mmp9 participates in cellular homing and migration, it might aid in blood vessel relocation. We examined the influence of short-term intermittent PTH administration on angiogenesis, Mmp9 secretion and the distance between blood vessels and bone. Mature (6- to 8-month-old) and middle-aged (10- to 12-month-old) male and female C57BL/6 mice were divided into three groups: control (CON), and 5 (5dPTH) and 10 days (10dPTH) of intermittent PTH administration. Mice were given PBS (50 µl day-1 ) or PTH(1-34) (43 µg kg-1 day-1 ). Frontal sections (5 µm thick) of the right distal femoral metaphysis were triple-immunolabelled to identify endothelial cells (anti-CD31), vascular smooth muscle cells (anti-αSMA) and Mmp9 (anti-Mmp9). Vascular density, Mmp9 density, area and localization, and blood vessel distance from bone were analysed. Blood vessels were analysed according to diameter: 1-29, 30-100 and 101-200 µm. Trabecular bone microarchitecture and bone static and dynamic properties were assessed. No main effects of age were observed for any variable. The density of CD31-labelled blood vessels 1-29 and 30-100 µm in diameter was higher (P < 0.05) and tended (P = 0.055) to be higher, respectively, in 10dPTH versus 5dPTH and CON. Mmp9 was augmented (P < 0.05) in 10dPTH versus the other groups. Mmp9 was closer (P < 0.05) to blood vessels 1-29 µm in diameter and furthest (P < 0.05) from bone. In conclusion, bone angiogenesis occurred by day 10 of intermittent PTH administration, coinciding with augmented Mmp9 secretion near the smallest blood vessels (1-29 µm in diameter).
Collapse
Affiliation(s)
- Seungyong Lee
- Department of Kinesiology, University of Texas at Arlington, Arlington, TX, USA
| | - Rhonda D Prisby
- Department of Kinesiology, University of Texas at Arlington, Arlington, TX, USA
| |
Collapse
|
|
22
|
Keller-Baruch J, Forgetta V, Manousaki D, Zhou S, Richards JB. Genetically Decreased Circulating Vascular Endothelial Growth Factor and Osteoporosis Outcomes: A Mendelian Randomization Study. J Bone Miner Res 2020; 35:649-656. [PMID: 31821593 DOI: 10.1002/jbmr.3937] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 11/11/2019] [Accepted: 12/01/2019] [Indexed: 11/10/2022]
Abstract
Vascular endothelial growth factor (VEGF) is important for bone formation and has been associated with osteoporosis in humans. Therefore, we conducted a two-sample Mendelian randomization study to test whether genetically decreased circulating VEGF was associated with decreased bone mineral density (BMD) and increased risk of fracture. Summary statistics from a genomewide association study (GWAS) meta-analysis of circulating VEGF level (n = 16,112) were used to identify 10 genetic variants explaining up to 52% of the variance in circulating VEGF levels. GWAS meta-analyses on dual-energy X-ray absorptiometry (DXA)-derived BMD of forearm, lumbar spine, and femoral neck (n = up to 32,735) and BMD estimated from heel calcaneus ultrasound (eBMD) (n = 426,824) were used to assess the effect of genetically lowered circulating VEGF levels on BMD. A GWAS meta-analysis including a total of 76,549 cases and 470,164 controls was used to assess the effect of genetically lowered circulating VEGF levels on risk of fracture. A natural log-transformed pg/mL decrease in circulating VEGF levels was not associated with a decrease in forearm BMD (0.02 standard deviation [SD], 95% confidence interval [CI] -0.024 to 0.064, p = 0.38), lumbar spine BMD (-0.005 SD, 95% CI -0.03 to 0.019, p = 0.67), femoral neck BMD (0.004 SD, 95% CI -0.017 to 0.026, p = 0.68), eBMD (-0.006 SD, 95% CI -0.012 to -0.001, p = 0.031) or risk of fracture (odds ratio = 0.99, 95% CI 0.98 to 1.0, p = 0.37) in inverse-variance-weighted Mendelian randomization analyses. Sensitivity analyses did not provide evidence that our results were influenced by pleiotropy. Genetically lowered circulating VEGF was not associated with a decrease in BMD or increased risk of fracture, suggesting that efforts to influence circulating VEGF level are unlikely to have beneficial effects on osteoporosis outcomes and that previous observational associations of circulating VEGF with BMD were influenced by confounding or reverse causation. © 2019 American Society for Bone and Mineral Research.
Collapse
Affiliation(s)
- Julyan Keller-Baruch
- Department of Human Genetics, McGill University, Montreal, Canada.,Centre for Clinical Epidemiology, Lady Davis Institute at the Jewish General Hospital, Montreal, Canada
| | - Vincenzo Forgetta
- Centre for Clinical Epidemiology, Lady Davis Institute at the Jewish General Hospital, Montreal, Canada
| | - Despoina Manousaki
- Department of Human Genetics, McGill University, Montreal, Canada.,Centre for Clinical Epidemiology, Lady Davis Institute at the Jewish General Hospital, Montreal, Canada
| | - Sirui Zhou
- Centre for Clinical Epidemiology, Lady Davis Institute at the Jewish General Hospital, Montreal, Canada.,Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
| | - J Brent Richards
- Department of Human Genetics, McGill University, Montreal, Canada.,Centre for Clinical Epidemiology, Lady Davis Institute at the Jewish General Hospital, Montreal, Canada.,Department of Twin Research, King's College London, London, UK
| |
Collapse
|
|
23
|
Gohin S, Javaheri B, Hopkinson M, Pitsillides AA, Arnett TR, Chenu C. Applied mechanical loading to mouse hindlimb acutely increases skeletal perfusion and chronically enhanced vascular porosity. J Appl Physiol (1985) 2020; 128:838-846. [PMID: 32163331 DOI: 10.1152/japplphysiol.00416.2019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Blood supply is essential for osteogenesis, yet its relationship to load-related increases in bone mass is poorly defined. Herein, we aim to investigate the link between load-induced osteogenesis and the blood supply (bone perfusion and vascular porosity) using an established osteogenic noninvasive model of axial loading. Accordingly, 12 N mechanical loads were applied to the right tibiae of six male C57BL6 mice at 10-12 wk of age, 3 times/wk for 2 wk. Skeletal perfusion was measured acutely (postloading) and chronically in loaded and contralateral, nonloaded hindlimbs by laser-Doppler imaging. Vascular and lacunar porosity of the cortical bone and tibia load-related changes in trabecular and cortical bone was measured by nanoCT and micro-CT, respectively. We found that the mean skeletal perfusion (loaded: nonloaded limb ratio) increased by 56% immediately following the first loading episode (vs. baseline, P < 0.01), and a similar increase was observed after all loading episodes, demonstrating that these acute responses were conserved for 2 wk of loading. Loading failed, however, to engender any significant chronic changes in mean perfusion between the beginning and the end of the experiment. In contrast, 2 wk of loading engendered an increased vascular canal number in the tibial cortical compartment (midshaft) and, as expected, also increased trabecular and cortical bone volumes and modified tibial architecture in the loaded limb. Our results indicate that each episode of loading both generates acute enhancement in skeletal blood perfusion and also stimulates chronic vascular architectural changes in the bone cortices, which coincide with load-induced increases in bone mass.NEW & NOTEWORTHY This study investigated modifications to the blood supply (bone perfusion and intracortical vascular canals) in mechanoadaptive responses in C57BL6 mice. Each episode of mechanical loading acutely increases skeletal perfusion. Two weeks of mechanical loading increased bone mass and cortical vascular canal number, while there was no chronic increase in hindlimb perfusion. Our findings suggest that the blood supply may participate in the processes that govern load-induced bone formation.
Collapse
Affiliation(s)
- Stephanie Gohin
- Department of Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom
| | - Behzad Javaheri
- Department of Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom
| | - Mark Hopkinson
- Department of Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom
| | | | - Timothy R Arnett
- Department of Cell and Developmental Biology, University College London, London, United Kingdom
| | - Chantal Chenu
- Department of Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom
| |
Collapse
|
|
24
|
Hanne NJ, Easter ED, Cole JH. Minimally invasive laser Doppler flowmetry is suitable for serial bone perfusion measurements in mice. Bone Rep 2019; 11:100231. [PMID: 31867412 PMCID: PMC6900537 DOI: 10.1016/j.bonr.2019.100231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 10/17/2019] [Accepted: 11/18/2019] [Indexed: 01/02/2023] Open
Abstract
In vivo laser Doppler flowmetry (LDF) has previously been used to quantify blood perfusion accurately at a single timepoint in the murine tibial metaphysis. However, this procedure entailed substantial disruption to soft tissues overlying the bone and caused notable localized inflammation for several weeks after the procedure, impeding serial measurements in the same mouse. In this study, we tested a less invasive technique to measure perfusion in the tibia with LDF and determined that it can be used serially in the same mouse without causing signs of inflammation or gait perturbations. Twenty 14-week-old C57Bl/6J mice were evenly divided into groups that either had daily treadmill exercise or remained sedentary. Within these activity groups, mice were evenly subdivided into groups that received LDF measurements either weekly or only once at the study endpoint. Bone perfusion was measured with LDF in the anteromedial region of the right tibial metaphysis. Serum concentrations of interleukin 6, incision site wound area, and interlimb coordination during gait were measured weekly for four weeks. Tibial perfusion did not differ significantly between exercise and sedentary groups within the weekly or endpoint-only LDF groups at any timepoint. Perfusion was significantly increased in the third week in the weekly LDF group relative to measurements in the second and fourth weeks. Ligation of the femoral artery caused consistent, rapid reductions in tibial perfusion, validating that LDF is sensitive to changes in tibial blood supply. Weekly LDF procedures did not adversely affect gait, as interlimb coordination during treadmill locomotion was similar between weekly and endpoint-only LDF groups at every timepoint. Images of the incision site show wound closure within one week, and serum concentrations of interleukin 6 were not significantly different between weekly and endpoint-only groups. Together, these findings demonstrate that our minimally invasive LDF technique is suitable for serial in vivo measurements of intraosseous blood perfusion without inducing localized inflammation or negatively affecting gait patterns in mice.
Collapse
Affiliation(s)
- Nicholas J Hanne
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA, and North Carolina State University, Raleigh, NC, USA
| | - Elizabeth D Easter
- Materials Science and Engineering, North Carolina State University, Raleigh, NC, USA
| | - Jacqueline H Cole
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA, and North Carolina State University, Raleigh, NC, USA
| |
Collapse
|
|
25
|
Sivan U, De Angelis J, Kusumbe AP. Role of angiocrine signals in bone development, homeostasis and disease. Open Biol 2019; 9:190144. [PMID: 31575330 PMCID: PMC6833221 DOI: 10.1098/rsob.190144] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Skeletal vasculature plays a central role in the maintenance of microenvironments for osteogenesis and haematopoiesis. In addition to supplying oxygen and nutrients, vasculature provides a number of inductive factors termed as angiocrine signals. Blood vessels drive recruitment of osteoblast precursors and bone formation during development. Angiogenesis is indispensable for bone repair and regeneration. Dysregulation of the angiocrine crosstalk is a hallmark of ageing and pathobiological conditions in the skeletal system. The skeletal vascular bed is complex, heterogeneous and characterized by distinct capillary subtypes (type H and type L), which exhibit differential expression of angiocrine factors. Furthermore, distinct blood vessel subtypes with differential angiocrine profiles differentially regulate osteogenesis and haematopoiesis, and drive disease states in the skeletal system. This review provides an overview of the role of angiocrine signals in bone during homeostasis and disease.
Collapse
Affiliation(s)
- Unnikrishnan Sivan
- The Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
| | - Jessica De Angelis
- The Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
| | - Anjali P Kusumbe
- The Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
| |
Collapse
|
|
26
|
The Effect of Exercise on the Prevention of Osteoporosis and Bone Angiogenesis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:8171897. [PMID: 31139653 PMCID: PMC6500645 DOI: 10.1155/2019/8171897] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 02/27/2019] [Accepted: 04/08/2019] [Indexed: 12/20/2022]
Abstract
Physical activity or appropriate exercise prevents the development of osteoporosis. However, the exact mechanism remains unclear although it is well accepted that exercise or mechanical loading regulates the hormones, cytokines, signaling pathways, and noncoding RNAs in bone. Accumulating evidence has shown that bone is a highly vascularized tissue, and dysregulation of vasculature is associated with many bone diseases such as osteoporosis or osteoarthritis. In addition, exercise or mechanical loading regulates bone vascularization in bone microenvironment via the modulation of angiogenic mediators, which play a crucial role in maintaining skeletal health. This review discusses the effects of exercise and its underlying mechanisms for osteoporosis prevention, as well as an angiogenic and osteogenic coupling in response to exercise.
Collapse
|
|
27
|
Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect. Stem Cells Int 2019; 2019:5750967. [PMID: 31065275 PMCID: PMC6466852 DOI: 10.1155/2019/5750967] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 12/30/2018] [Accepted: 01/13/2019] [Indexed: 02/05/2023] Open
Abstract
Reconstruction of segmental bone defects poses a tremendous challenge for both orthopedic clinicians and scientists, since bone rehabilitation is requisite substantially and may be beyond the capacity of self-healing. Bone marrow mesenchymal stem cells (BMSCs) have been identified as an optimal progenitor cell source to facilitate bone repair since they have a higher ability for proliferation and are more easily accessible than mature osteoblastic cells. In spite of the potential of BMSCs in regeneration medicine, particularly for bone reconstruction, noteworthy limitations still remain in previous application of BMSCs, including the amount of cells that could be recruited, the compromised bone migration of grafted cells, reduced proliferation and osteoblastic differentiation ability, and likely tumorigenesis. Our current work demonstrates that BMSCs transplanted through the caudal vein can be mobilized by erythropoietin (EPO) to the bone defect area and participate in regeneration of new bone. Based on the histological analysis and micro-CT findings of this study, EPO can dramatically promote the effects on the osteogenesis and angiogenesis efficiency of BMSCs in vivo. Animals that underwent EPO+BMSC administration demonstrated a remarkable increase in new bone formation, tissue structure organization, new vessel density, callus formation, and bone mineral density (BMD) compared with the BMSCs alone and control groups. At the biomechanical level, we demonstrated that combing transplantation of EPO and BMSCs enhances bone defect reconstruction by increasing the strength of the diaphysis, making it less fragile. Therefore, combination therapy using EPO infusion and BMSC transplantation may be a new therapeutic strategy for the reconstruction of segmental bone defect.
Collapse
|
|
28
|
Agoston DV, Kamnaksh A. Protein biomarkers of epileptogenicity after traumatic brain injury. Neurobiol Dis 2019; 123:59-68. [PMID: 30030023 PMCID: PMC6800147 DOI: 10.1016/j.nbd.2018.07.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Revised: 07/10/2018] [Accepted: 07/16/2018] [Indexed: 12/15/2022] Open
Abstract
Traumatic brain injury (TBI) is a major risk factor for acquired epilepsy. Post-traumatic epilepsy (PTE) develops over time in up to 50% of patients with severe TBI. PTE is mostly unresponsive to traditional anti-seizure treatments suggesting distinct, injury-induced pathomechanisms in the development of this condition. Moderate and severe TBIs cause significant tissue damage, bleeding, neuron and glia death, as well as axonal, vascular, and metabolic abnormalities. These changes trigger a complex biological response aimed at curtailing the physical damage and restoring homeostasis and functionality. Although a positive correlation exists between the type and severity of TBI and PTE, there is only an incomplete understanding of the time-dependent sequelae of TBI pathobiologies and their role in epileptogenesis. Determining the temporal profile of protein biomarkers in the blood (serum or plasma) and cerebrospinal fluid (CSF) can help to identify pathobiologies underlying the development of PTE, high-risk individuals, and disease modifying therapies. Here we review the pathobiological sequelae of TBI in the context of blood- and CSF-based protein biomarkers, their potential role in epileptogenesis, and discuss future directions aimed at improving the diagnosis and treatment of PTE.
Collapse
Affiliation(s)
- Denes V Agoston
- Department of Anatomy, Physiology and Genetics, Uniformed Services University, Bethesda, MD, USA.
| | - Alaa Kamnaksh
- Department of Anatomy, Physiology and Genetics, Uniformed Services University, Bethesda, MD, USA
| |
Collapse
|
|
29
|
|
|
30
|
Prisby RD. Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone. J Endocrinol 2017; 235:R77-R100. [PMID: 28814440 PMCID: PMC5611884 DOI: 10.1530/joe-16-0666] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 08/16/2017] [Indexed: 12/25/2022]
Abstract
Bone tissue is highly vascularized due to the various roles bone blood vessels play in bone and bone marrow function. For example, the vascular system is critical for bone development, maintenance and repair and provides O2, nutrients, waste elimination, systemic hormones and precursor cells for bone remodeling. Further, bone blood vessels serve as egress and ingress routes for blood and immune cells to and from the bone marrow. It is becoming increasingly clear that the vascular and skeletal systems are intimately linked in metabolic regulation and physiological and pathological processes. This review examines how agents such as mechanical loading, parathyroid hormone, estrogen, vitamin D and calcitonin, all considered anabolic for bone, have tremendous impacts on the bone vasculature. In fact, these agents influence bone blood vessels prior to influencing bone. Further, data reveal strong associations between vasodilator capacity of bone blood vessels and trabecular bone volume, and poor associations between estrogen status and uterine mass and trabecular bone volume. Additionally, this review highlights the importance of the bone microcirculation, particularly the vascular endothelium and NO-mediated signaling, in the regulation of bone blood flow, bone interstitial fluid flow and pressure and the paracrine signaling of bone cells. Finally, the vascular endothelium as a mediator of bone health and disease is considered.
Collapse
Affiliation(s)
- Rhonda D Prisby
- Department of KinesiologyUniversity of Texas at Arlington, Arlington, Texas, USA
| |
Collapse
|
|
31
|
Sun T, Zhou K, Liu M, Guo X, Qu Y, Cui W, Shao Z, Zhang X, Xu S. Loading of BMP-2-related peptide onto three-dimensional nano-hydroxyapatite scaffolds accelerates mineralization in critical-sized cranial bone defects. J Tissue Eng Regen Med 2017; 12:864-877. [PMID: 27885807 DOI: 10.1002/term.2371] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 07/14/2016] [Accepted: 11/09/2016] [Indexed: 01/08/2023]
Abstract
Extrusion free-forming, as a rapid prototyping technique, is extensively applied in fabricating ceramic material in bone tissue engineering. To improve the osteoinductivity of nano-hydroxyapatite (nHA) scaffold fabricated by extrusion free-forming, in this study, we incorporated a new peptide (P28) and optimized the superficial microstructure after shaping by controlling the sintering temperature. P28, a novel bone morphogenic protein 2 (BMP-2)-related peptide, was designed in this study. Analysis of the structure, physicochemical properties and release kinetics of P28 from nHA sintered at temperatures ranging from 1000 °C to 1400 °C revealed that nHA sintered at 1000 °C had higher porosity, preferable pore size and better capacity to control P28 release than that sintered at other temperatures. Moreover, the nHA scaffold sintered at 1000 °C with P28 showed improved adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells compared with scaffolds lacking P28 or BMP-2. In vivo, nHA scaffolds sintered at 1000 °C with P28 or BMP-2 induced greater bone regeneration in critical-sized rat cranial defects at 6 and 12 weeks post-implantation compared with scaffolds lacking P28 or BMP-2. Thus, nHA scaffolds sintered at 1000 °C and loaded with P28 may be excellent biomaterials for bone tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.
Collapse
Affiliation(s)
- Tingfang Sun
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kui Zhou
- State Key Lab of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Man Liu
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiaodong Guo
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yanzhen Qu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wei Cui
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - ZengWu Shao
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xianglin Zhang
- State Key Lab of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Shuyun Xu
- Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| |
Collapse
|
|
32
|
Gnyubkin V, Guignandon A, Laroche N, Vanden-Bossche A, Malaval L, Vico L. High-acceleration whole body vibration stimulates cortical bone accrual and increases bone mineral content in growing mice. J Biomech 2016; 49:1899-1908. [PMID: 27178020 DOI: 10.1016/j.jbiomech.2016.04.031] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 04/26/2016] [Accepted: 04/27/2016] [Indexed: 11/17/2022]
Abstract
Whole body vibration (WBV) is a promising tool for counteracting bone loss. Most WBV studies on animals have been performed at acceleration <1g and frequency between 30 and 90Hz. Such WBV conditions trigger bone growth in osteopenia models, but not in healthy animals. In order to test the ability of WBV to promote osteogenesis in young animals, we exposed seven-week-old male mice to vibration at 90Hz and 2g peak acceleration for 15min/day, 5 days/week. We examined the effects on skeletal tissues with micro-computed tomography and histology. We also quantified bone vascularization and mechanosensitive osteocyte proteins, sclerostin and DMP1. Three weeks of WBV resulted in an increase of femur cortical thickness (+5%) and area (+6%), associated with a 25% decrease of sclerostin expression, and 35% increase of DMP1 expression in cortical osteocytes. Mass-structural parameters of trabecular bone were unaltered in femur or vertebra, while osteoclastic parameters and bone formation rate were increased at both sites. Three weeks of WBV resulted in higher blood vessel numbers (+23%) in the distal femoral metaphysis. After 9-week WBV, we have not observed the difference in structural cortical or trabecular parameters. However, the tissue mineral density of cortical bone was increased by 2.5%. Three or nine weeks of 2g/90Hz WBV treatment did not affect longitudinal growth rate or body weight increase under our experimental conditions, indicating that these are safe to use. These results validate a potential of 2g/90Hz WBV to stimulate trabecular bone cellular activity, accelerate cortical bone growth, and increase bone mineral density.
Collapse
Affiliation(s)
- Vasily Gnyubkin
- INSERM U1059, 42023 Saint-Etienne, France; Université de Lyon, 42023 Saint-Etienne, France
| | - Alain Guignandon
- INSERM U1059, 42023 Saint-Etienne, France; Université de Lyon, 42023 Saint-Etienne, France
| | - Norbert Laroche
- INSERM U1059, 42023 Saint-Etienne, France; Université de Lyon, 42023 Saint-Etienne, France
| | - Arnaud Vanden-Bossche
- INSERM U1059, 42023 Saint-Etienne, France; Université de Lyon, 42023 Saint-Etienne, France
| | - Luc Malaval
- INSERM U1059, 42023 Saint-Etienne, France; Université de Lyon, 42023 Saint-Etienne, France
| | - Laurence Vico
- INSERM U1059, 42023 Saint-Etienne, France; Université de Lyon, 42023 Saint-Etienne, France.
| |
Collapse
|
|
33
|
Boudenot A, Maurel DB, Pallu S, Ingrand I, Boisseau N, Jaffré C, Portier H. Quick benefits of interval training versus continuous training on bone: a dual-energy X-ray absorptiometry comparative study. Int J Exp Pathol 2016; 96:370-7. [PMID: 26754273 DOI: 10.1111/iep.12155] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Accepted: 09/06/2015] [Indexed: 12/01/2022] Open
Abstract
To delay age-related bone loss, physical activity is recommended during growth. However, it is unknown whether interval training is more efficient than continuous training to increase bone mass both quickly and to a greater extent. The aim of this study was to compare the effects of a 10-week interval training regime with a 14-week continuous training regime on bone mineral density (BMD). Forty-four male Wistar rats (8 weeks old) were separated into four groups: control for 10 weeks (C10), control for 14 weeks (C14), moderate interval training for 10 weeks (IT) and moderate continuous training for 14 weeks (CT). Rats were exercised 1 h/day, 5 day/week. Body composition and BMD of the whole body and femur respectively were assessed by dual-energy X-ray absorptiometry at baseline and after training to determine raw gain and weight-normalized BMD gain. Both trained groups had lower weight and fat mass gain when compared to controls. Both trained groups gained more BMD compared to controls when normalized to body weight. Using a 30% shorter training period, the IT group showed more than 20% higher whole body and femur BMD gains compared to the CT. Our data suggest that moderate IT was able to produce faster bone adaptations than moderate CT.
Collapse
Affiliation(s)
- Arnaud Boudenot
- Movement to Health - Euromov, UFR STAPS, Université de Montpellier 1, Montpellier, France.,UMR-S658 INSERM, Université d'Orléans, Orléans, France
| | - Delphine B Maurel
- UMR-S658 INSERM, Université d'Orléans, Orléans, France.,Laboratory of Oral Biology, School of Dentistry, Kansas City, MO, USA
| | - Stéphane Pallu
- UMR-S658 INSERM, Université d'Orléans, Orléans, France.,UMR 7052 Laboratory for Osteoarticular Bioengineering and Bioimaging, CNRS, Univ Paris Diderot, Sorbonne Paris Cité, École nationale vétérinaire d'Alfort, Paris, France.,Université d'Orléans, Orléans, France
| | - Isabelle Ingrand
- Epidémiologie et Biostatistique, Inserm CIC 802, CHU Poitiers, Université de Poitiers, Poitiers, France
| | - Nathalie Boisseau
- Laboratory of Metabolic Adaptations to Exercise under Physiological and Pathological Conditions, EA 3533, Clermont University, Blaise Pascal University BP 10448, Clermont-Ferrand, France
| | - Christelle Jaffré
- UMR-S658 INSERM, Université d'Orléans, Orléans, France.,EA 3300, Adaptations Physiologiques à l'Exercice et Réadaptation à l'Effort, UFR des Sciences du Sport, Université de Picardie Jules Verne, 80025, Amiens, France
| | - Hugues Portier
- UMR 7052 Laboratory for Osteoarticular Bioengineering and Bioimaging, CNRS, Univ Paris Diderot, Sorbonne Paris Cité, École nationale vétérinaire d'Alfort, Paris, France.,Université d'Orléans, Orléans, France
| |
Collapse
|
|
34
|
Gnyubkin V, Guignandon A, Laroche N, Vanden-Bossche A, Normand M, Lafage-Proust MH, Vico L. Effects of chronic hypergravity: from adaptive to deleterious responses in growing mouse skeleton. J Appl Physiol (1985) 2015; 119:908-17. [PMID: 26228999 DOI: 10.1152/japplphysiol.00364.2015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Accepted: 07/27/2015] [Indexed: 11/22/2022] Open
Abstract
One of the most important but least studied environmental factors playing a major role in bone physiology is gravity. While the knowledge of deleterious effects of microgravity on the skeleton is expanding, little is known about hypergravity and its osteogenic potential. Centrifugation was used to assess effects of 21-day continuous 2- or 3-g acceleration on femur and L2-vertebra of 7-wk-old male C57BL/6 mice. Under 3 g, body mass growth slowed down, and deleterious skeletal effects were found (P < 0.05 compared with control): cortical thinning, osteoclasts surface increase (+41% in femur, +20% in vertebra), and bone formation rate decrease (-34% in femur, -38% in vertebra). A 2-g centrifugation did not reduce body mass and improved trabecular volume (+18% in femur, +13% in vertebra) and microarchitecture (+32% connectivity density in femur, +9% trabecular thickness in vertebra, P < 0.05 compared with control). Centrifugation at 2 g also decreased osteoclast surfaces (-36% in femur, -16% in vertebra) and increased the extent of mineralized surfaces (+31% in femur, +48% in vertebra, P < 0.05 compare to control). Quantitative immunohistochemistry revealed an increase of dentin matrix acidic phosphoprotein 1 (DMP1) and decrease of sclerostin (+60% and -35% respectively, P < 0.001 compared with control) in the femur cortex of 2-g mice. In the distal femur metaphysis, the number and volume of blood vessels increased by 22 and 44%, respectively (P < 0.05 compared with control). In conclusion, the effects of continuous hypergravity were bone compartment-specific and depended on the gravity level, with a threshold between beneficial 2-g and deleterious 3-g effects.
Collapse
Affiliation(s)
- Vasily Gnyubkin
- Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| | - Alain Guignandon
- Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| | - Norbert Laroche
- Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| | - Arnaud Vanden-Bossche
- Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| | - Myriam Normand
- Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| | - Marie-Hélène Lafage-Proust
- Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| | - Laurence Vico
- Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| |
Collapse
|
|
35
|
Zhang J, He F, Zhang W, Zhang M, Yang H, Luo ZP. Mechanical force enhanced bony formation in defect implanted with calcium sulphate cement. Bone Res 2015; 3:14048. [PMID: 26273532 PMCID: PMC4472145 DOI: 10.1038/boneres.2014.48] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2014] [Revised: 08/24/2014] [Accepted: 10/25/2014] [Indexed: 11/13/2022] Open
Abstract
To improve the osteogenic property of bone repairing materials and to accelerate bone healing are major tasks in bone biomaterials research. The objective of this study was to investigate if the mechanical force could be used to accelerate bone formation in a bony defect in vivo. The calcium sulfate cement was implanted into the left distal femoral epiphyses surgically in 16 rats. The half of rats were subjected to external mechanical force via treadmill exercise, the exercise started at day 7 postoperatively for 30 consecutive days and at a constant speed 8 m·min−1 for 45 min·day−1, while the rest served as a control. The rats were scanned four times longitudinally after surgery using microcomputed tomography and newly formed bone was evaluated. After sacrificing, the femurs had biomechanical test of three-point bending and histological analysis. The results showed that bone healing under mechanical force were better than the control with residual defect areas of 0.64±0.19 mm2 and 1.78±0.39 mm2 (P<0.001), and the ultimate loads to failure under mechanical force were 69.56±4.74 N, stronger than the control with ultimate loads to failure of 59.17±7.48 N (P=0.039). This suggests that the mechanical force might be used to improve new bone formation and potentially offer a clinical strategy to accelerate bone healing.
Collapse
Affiliation(s)
- Jie Zhang
- Department of Orthopedic Surgery, the 1st Affiliated Hospital, and Orthopedic Institute, Soochow University , Suzhou, China
| | - Fan He
- Department of Orthopedic Surgery, the 1st Affiliated Hospital, and Orthopedic Institute, Soochow University , Suzhou, China
| | - Wen Zhang
- Department of Orthopedic Surgery, the 1st Affiliated Hospital, and Orthopedic Institute, Soochow University , Suzhou, China
| | - Meng Zhang
- Department of Orthopedic Surgery, the 1st Affiliated Hospital, and Orthopedic Institute, Soochow University , Suzhou, China
| | - Huilin Yang
- Department of Orthopedic Surgery, the 1st Affiliated Hospital, and Orthopedic Institute, Soochow University , Suzhou, China
| | - Zong-Ping Luo
- Department of Orthopedic Surgery, the 1st Affiliated Hospital, and Orthopedic Institute, Soochow University , Suzhou, China
| |
Collapse
|
|
36
|
Tomlinson RE, Schmieder AH, Quirk JD, Lanza GM, Silva MJ. Antagonizing the αv β3 integrin inhibits angiogenesis and impairs woven but not lamellar bone formation induced by mechanical loading. J Bone Miner Res 2014; 29:1970-80. [PMID: 24644077 PMCID: PMC4323187 DOI: 10.1002/jbmr.2223] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Revised: 02/25/2014] [Accepted: 02/27/2014] [Indexed: 12/26/2022]
Abstract
Angiogenesis and osteogenesis are critically linked, although the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non-damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid-diaphysis of the adult rat forelimb. αv β3 integrin-targeted nanoparticles or vehicle was injected intravenously after mechanical loading. β3 integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF-loaded limbs was increased compared with non-loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF- and LBF-loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post-yield behavior. These results demonstrate that αv β3 integrin-mediated angiogenesis is critical for recovering fracture resistance after bone injury but is not required for bone modeling after modest mechanical strain. © 2014 American Society for Bone and Mineral Research.
Collapse
Affiliation(s)
- Ryan E. Tomlinson
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University in St. Louis, Saint Louis, MO, USA
- Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, USA
| | - Anne H. Schmieder
- Department of Medicine, Division of Cardiology, Washington University in St. Louis, Saint Louis, MO, USA
| | - James D. Quirk
- Department of Radiology, Washington University in St. Louis, Saint Louis, MO, USA
| | - Gregory M. Lanza
- Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, USA
- Department of Medicine, Division of Cardiology, Washington University in St. Louis, Saint Louis, MO, USA
| | - Matthew J. Silva
- Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University in St. Louis, Saint Louis, MO, USA
- Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, USA
| |
Collapse
|
|
37
|
Roche B, Vanden-Bossche A, Malaval L, Normand M, Jannot M, Chaux R, Vico L, Lafage-Proust MH. Parathyroid hormone 1-84 targets bone vascular structure and perfusion in mice: impacts of its administration regimen and of ovariectomy. J Bone Miner Res 2014; 29:1608-18. [PMID: 24496950 DOI: 10.1002/jbmr.2191] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 01/21/2014] [Accepted: 01/26/2014] [Indexed: 12/22/2022]
Abstract
Bone vessel functions during bone remodeling are poorly understood. They depend on both vessel network structure and vasomotor regulation. Parathyroid hormone (PTH) is a systemic vasodilator that may modulate microvascularization. Moreover, although intermittent PTH is anti-osteoporotic, continuous PTH administration can be catabolic for bone. Finally, ovariectomy (OVX) reduces bone perfusion and vessel density in mice. We reasoned that the effects of PTH on bone vascularization might depend on its administration regimen and be impacted by ovariectomy. A 100-µg/kg PTH 1-84 daily dose was administered for 15 days to 4-month-old female C57BL/6 mice, either as daily sc injection (iPTH) or continuously (cPTH; ALZET minipump). Blood pressure (BP) and tibia bone perfusion were measured in vivo with a laser Doppler device. Histomorphometry of bone and barium-contrasted vascular network were performed on the same tibia. Compared with untreated controls, both iPTH and cPTH increased bone formation but had opposite effects on resorption. Both iPTH and cPTH were slightly angiogenic. Intermittent PTH increased microvessel size (+48%, p < 0.001), whereas cPTH decreased it (-29%, p = 0.009). iPTH increased bone perfusion (27%, p < 0.001) with no change in BP, whereas cPTH did not. The vascular effects of a 15-day iPTH treatment were analyzed in OVX mice and compared with sham-operated and OVX untreated controls. Two other anti-osteoporotic drugs, zoledronate (one injection, 70 µg/kg) and propranolol, (5 mg/kg/d) were tested in OVX mice. Although no change in bone mass was observed, iPTH stimulated bone formation and prevented the OVX-induced reduction in bone perfusion and vessel density. Both zoledronate and propranolol strongly lowered bone turnover, but surprisingly, zoledronate prevented OVX-induced reduction in bone perfusion but propranolol did not. Our integrative approach thus demonstrates that the effects of PTH on bone vessel structure and function depend on its mode of administration as well as on the HPG-axis hormonal status, and that OVX-induced vascular changes are prevented by iPTH.
Collapse
Affiliation(s)
- Bernard Roche
- INSERM U1059, Lab Biologie Intégrée du Tissu Osseux, Université de Lyon, Saint-Etienne, France
| | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Smith JNP, Calvi LM. Concise review: Current concepts in bone marrow microenvironmental regulation of hematopoietic stem and progenitor cells. Stem Cells 2014; 31:1044-50. [PMID: 23509002 DOI: 10.1002/stem.1370] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Accepted: 01/29/2013] [Indexed: 12/20/2022]
Abstract
Hematopoietic stem cell (HSC) behavior is governed in large part by interactions of the blood system with the bone microenvironment. Increasing evidence demonstrates the profound role the local HSC microenvironment or niche plays in normal stem cell function, in therapeutic activation and in the setting of malignancy. A number of cellular and molecular components of the microenvironment have been identified thus far, several of which are likely to provide exciting therapeutic targets in the near future. Clinically effective strategies for niche manipulation, however, require careful study of the interaction of these niche components. Some of the key findings defining these regulatory interactions are explored in this concise review, with special emphasis on potential translational applications.
Collapse
Affiliation(s)
- Julianne N P Smith
- Department of Pathology and Laboratory MedicineUniversity of Rochester School of Medicine, Rochester, New York 14642, USA
| | | |
Collapse
|
|
39
|
Marenzana M, Arnett TR. The Key Role of the Blood Supply to Bone. Bone Res 2013; 1:203-15. [PMID: 26273504 DOI: 10.4248/br201303001] [Citation(s) in RCA: 230] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Accepted: 07/22/2013] [Indexed: 12/16/2022] Open
Abstract
The importance of the vascular supply for bone is well-known to orthopaedists but is still rather overlooked within the wider field of skeletal research. Blood supplies oxygen, nutrients and regulatory factors to tissues, as well as removing metabolic waste products such as carbon dioxide and acid. Bone receives up to about 10% of cardiac output, and this blood supply permits a much higher degree of cellularity, remodelling and repair than is possible in cartilage, which is avascular. The blood supply to bone is delivered to the endosteal cavity by nutrient arteries, then flows through marrow sinusoids before exiting via numerous small vessels that ramify through the cortex. The marrow cavity affords a range of vascular niches that are thought to regulate the growth and differentiation of hematopoietic and stromal cells, in part via gradients of oxygen tension. The quality of vascular supply to bone tends to decline with age and may be compromised in common pathological settings, including diabetes, anaemias, chronic airway diseases and immobility, as well as by tumours. Reductions in vascular supply are associated with bone loss. This may be due in part to the direct effects of hypoxia, which blocks osteoblast function and bone formation but causes reciprocal increases in osteoclastogenesis and bone resorption. Common regulatory factors such as parathyroid hormone or nitrates, both of which are potent vasodilators, might exert their osteogenic effects on bone via the vasculature. These observations suggest that the bone vasculature will be a fruitful area for future research.
Collapse
Affiliation(s)
- Massimo Marenzana
- Department of Bioengineering, Imperial College London and Kennedy Institute of Rheumatology, University of Oxford , UK
| | - Timothy R Arnett
- Department of Cell and Developmental Biology, University College London , UK
| |
Collapse
|
|
40
|
Chen W, Liu J, Manuchehrabadi N, Weir MD, Zhu Z, Xu HHK. Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects. Biomaterials 2013; 34:9917-25. [PMID: 24054499 DOI: 10.1016/j.biomaterials.2013.09.002] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Accepted: 09/02/2013] [Indexed: 02/08/2023]
Abstract
Human umbilical cord mesenchymal stem cells (hUCMSCs) are inexhaustible and can be harvested at a low cost without an invasive procedure. However, there has been no report on comparing hUCMSCs with human bone marrow MSCs (hBMSCs) for bone regeneration in vivo. The aim of this study was to investigate hUCMSC and hBMSC seeding on macroporous calcium phosphate cement (CPC), and to compare their bone regeneration in critical-sized cranial defects in rats. Cell attachment, osteogenic differentiation and mineral synthesis on RGD-modified macroporous CPC were investigated in vitro. Scaffolds with cells were implanted in 8-mm defects of athymic rats. Bone regeneration was investigated via micro-CT and histological analysis at 4, 12, and 24 weeks. Three groups were tested: CPC with hUCMSCs, CPC with hBMSCs, and CPC control without cells. Percentage of live cells and cell density on CPC in vitro were similarly good for hUCMSCs and hBMSCs. Both cells had high osteogenic expressions of alkaline phosphatase, osteocalcin, collagen I, and Runx2. Bone mineral density and trabecular thickness in hUCMSC and hBMSC groups in vivo were greater than those of CPC control group. New bone amount for hUCMSC-CPC and hBMSC-CPC constructs was increased by 57% and 88%, respectively, while blood vessel density was increased by 15% and 20%, than CPC control group at 24 weeks. hUCMSC-CPC and hBMSC-CPC groups generally had statistically similar bone mineral density, new bone amount and vessel density. In conclusion, hUCMSCs seeded on CPC were shown to match the bone regeneration efficacy of hBMSCs in vivo for the first time. Both hUCMSC-CPC and hBMSC-CPC constructs generated much more new bone and blood vessels than CPC without cells. Macroporous RGD-grafted CPC with stem cell seeding is promising for craniofacial and orthopedic repairs.
Collapse
Affiliation(s)
- Wenchuan Chen
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA
| | | | | | | | | | | |
Collapse
|
|
41
|
Scarano A, Perrotti V, Artese L, Degidi M, Degidi D, Piattelli A, Iezzi G. Blood vessels are concentrated within the implant surface concavities: a histologic study in rabbit tibia. Odontology 2013; 102:259-66. [PMID: 23783569 DOI: 10.1007/s10266-013-0116-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2012] [Accepted: 04/22/2013] [Indexed: 12/27/2022]
Abstract
Angiogenesis plays a key role in bone formation and maintenance. Bone formation has been reported to initiate in the concavities rather than the convexities in a hydroxyapatite substratum and the implant threads of dental implants. The aim of the present study was to evaluate the number of the blood vessels inside the concavities and around the convexities of the threads of implants in a rabbit tibia model. A total of 32 thread-shaped implants blasted with apatitic calcium phosphate (TCP/HA blend) (Resorbable Blast Texturing, RBT) (Maestro, BioHorizons(®), Birmingham, AL, USA) were inserted in 8 rabbits. Each rabbit received 4 implants, 2 in the right and 2 in left tibia. Implants were retrieved after 1, 2, 4, and 8 weeks and treated to obtain thin ground sections. Statistically significant differences were found in the number of vessels that had formed in the concavities rather than the convexities of the implants after 1 (p = 0.000), and 2 weeks (p = 0.000), whilst no significant differences after 4 (p = 0.546) and 8 weeks (p = 0.275) were detected. The present results supported the hypothesis that blood vessel formation was stimulated by the presence of the concavities, which may provide a suitable environment in which mechanical forces, concentrations and gradients of chemotactic molecules and blood clot retention may all drive vascular and bone cell migration.
Collapse
Affiliation(s)
- Antonio Scarano
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via F. Sciucchi 63, 66100, Chieti, Italy
| | | | | | | | | | | | | |
Collapse
|
|
42
|
Buffoli B, Boninsegna R, Rezzani R, Poli PP, Santoro F, Rodella LF. Histomorphometrical evaluation of fresh frozen bone allografts for alveolar bone reconstruction: preliminary cases comparing femoral head with iliac crest grafts. Clin Implant Dent Relat Res 2013; 15:791-8. [PMID: 23294489 DOI: 10.1111/cid.12028] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
PURPOSE In the past few years, the use of fresh frozen bone (FFB) grafts has significantly increased. The aim of this study was to evaluate the reconstruction of alveolar bone using femoral head and iliac crest FFB grafts. MATERIALS AND METHODS The study included 10 patients who need endosseous implant insertion in severe atrophic maxillae. The patients were treated with FFB grafts collected from the femoral head or iliac crest. Bone regeneration was evaluated 6 months after surgery by macroscopic and microscopic analyses. RESULTS Our results showed good regenerative capacity, both with the FFB from the femoral head and iliac crest. In particular, similar percentages of new-bone formation and graft residual were observed, whereas differences between the percentage of total bone (higher for the iliac crest) and the percentage of non-mineralized tissue (higher for the femoral head) were present. A significantly higher percentage of CD34-positive vessels in the FFB allograft from the femoral head than in the iliac crest were observed. CONCLUSIONS These findings suggest that FFB allografts could represent a reliable option in oral and maxillofacial surgery. Nevertheless, differences between the use of femoral head or iliac crest bone allografts linked with their different structures should be considered for a more effective surgery.
Collapse
Affiliation(s)
- Barbara Buffoli
- Human Anatomy, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | | | | | | | | | | |
Collapse
|
|
43
|
Soki FN, Li X, Berry J, Koh A, Sinder BP, Qian X, Kozloff KM, Taichman RS, McCauley LK. The effects of zoledronic acid in the bone and vasculature support of hematopoietic stem cell niches. J Cell Biochem 2013; 114:67-78. [PMID: 22833499 PMCID: PMC3593195 DOI: 10.1002/jcb.24301] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2012] [Accepted: 07/17/2012] [Indexed: 12/24/2022]
Abstract
Hematopoietic stem cells (HSC) are maintained in a tightly regulated bone microenvironment constituted by a rich milieu of cells. Bone cells such as osteoblasts are associated with niche maintenance as regulators of the endosteal microenvironment. Bone remodeling also plays a role in HSC mobilization although it is poorly defined. The effects of zoledronic acid (ZA), a potent bisphosphonate that inhibits bone resorption, were investigated on bone marrow cell populations focusing on HSCs, and the endosteal and vascular niches in bone. ZA treatment significantly increased bone volume and HSCs in both young and adult mice (4 week and 4 month old, respectively). ZA increased vessel numbers with no overall change in vascular volume in bones of young and had no effect on vasculature in adult mice. Since both young and adult mice had increased HSCs and bone mass with differing vasculature responses, this suggests that ZA indirectly supports HSCs via the osteoblastic niche and not the vascular niche. Additionally, gene expression in Lin- cells demonstrated increased expression of self-renewal-related genes Bmi1 and Ink4a suggesting a role of ZA in the modulation of cell commitment and differentiation toward a long-term self-renewing cell. Genes that support the osteoblastic niche, BMP2 and BMP6 were also augmented in ZA treated mice. In conclusion, ZA-induced HSC expansion occurs independent of the vascular niche via indirect modulation of the osteoblastic niche.
Collapse
Affiliation(s)
- Fabiana N. Soki
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan
| | - Xin Li
- Basic Science and Craniofacial Biology, College of Dentistry, New York University, New York, New York
| | - Janice Berry
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan
| | - Amy Koh
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan
| | - Benjamin P. Sinder
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Xu Qian
- Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan
| | - Kenneth M. Kozloff
- Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Russell S. Taichman
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan
| | - Laurie K. McCauley
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan
- Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan
| |
Collapse
|
|
44
|
Sengul A, Santisuk R, Xing W, Kesavan C. Systemic administration of an antagomir designed to inhibit miR-92, a regulator of angiogenesis, failed to modulate skeletal anabolic response to mechanical loading. Physiol Res 2012; 62:221-6. [PMID: 23234410 DOI: 10.33549/physiolres.932410] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The goal of this study is to evaluate if promotion of angiogenesis by systemic treatment with an antagomir against miR-92a, a well established inhibitor of angiogenesis, will maximize the benefits of exercise on bone. Ten week old female C57BL6/J mice were subjected to two weeks of external load by four point bending. During the first week of mechanical loading (ML), mice were injected (2.7 mg/kg of bodyweight) with antagomir against miR-92 or control antagomir (3 alternate days via retro-orbital). No difference in tissues weights (heart, kidney, liver) were found in mice treated with miR-92 vs. control antagomir suggesting no side effects. Two weeks of ML increased tibia TV, BV/TV and density by 6-15 %, as expected, in the control antagomir treated mice. Similar increases in the above parameters (7-16 %) were also seen in mice treated miR-92 antagomir. Administration of miR-92 antagomir was effective in reducing levels of mir-92 in heart, liver and skeletal muscle and in contrast, expression levels of two other microRNA's miR-93 and miR-20a remain constant, thus suggesting specificity of the antagomir used. Surprisingly, we failed to detect significant changes in the expression levels of vascular genes (VEGF, CD31 and Tie2) in heart, liver or skeletal muscle. Based on these findings, we conclude that systemic administration of antagomir against miR-92 while reduced expression levels of miR-92 in the tissues; it did not significantly alter either angiogenic or osteogenic response, thus suggesting possible redundancy in miR-92 regulation of angiogenesis.
Collapse
Affiliation(s)
- A Sengul
- Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA, USA
| | | | | | | |
Collapse
|
|
45
|
Treatment of mandibular atrophy by an equine bone substitute: an immunohistochemical study in man. ACTA ACUST UNITED AC 2012. [DOI: 10.1016/j.ios.2012.03.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
|
|
46
|
Clarkin CE, Gerstenfeld LC. VEGF and bone cell signalling: an essential vessel for communication? Cell Biochem Funct 2012; 31:1-11. [PMID: 23129289 DOI: 10.1002/cbf.2911] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2012] [Revised: 08/31/2012] [Accepted: 09/10/2012] [Indexed: 01/17/2023]
Abstract
Vascular endothelial growth factor (VEGF) is an endothelial cell survival factor and is required for effective coupling of angiogenesis and osteogenesis. Although central to bone homeostasis, repair and the pathobiology that affect these processes, the precise mechanisms coupling endothelial cell function within bone formation and remodelling remain unclarified. This review will (i) focus on the potential directionality of VEGF signalling in adult bone by identifying the predominant source of VEGF within the bone microenvironment, (ii) will summarize current VEGF receptor expression studies by bone cells and (iii) will provide evidence for a role for VEGF signalling during postnatal repair and osteoporosis. A means of understanding the directionality of VEGF signalling in adult bone would allow us to most effectively target angiogenic pathways in diseases characterized by changes in bone remodelling rates and enhance bone repair when compromised.
Collapse
Affiliation(s)
- Claire E Clarkin
- Centre for Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.
| | | |
Collapse
|
|
47
|
Holstein JH, Becker SC, Fiedler M, Scheuer C, Garcia P, Histing T, Klein M, Menger MD, Pohlemann T. Increased exercise after stable closed fracture fixation does not affect fracture healing in mice. J Biomech 2012; 45:1299-304. [PMID: 22336197 DOI: 10.1016/j.jbiomech.2012.01.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2011] [Revised: 01/18/2012] [Accepted: 01/29/2012] [Indexed: 11/16/2022]
Abstract
PURPOSE The aim of the present study was to evaluate the systemic biological effect of increased exercise on bone repair after stable fracture fixation. METHODS Two groups of SKH-1h mice were studied. Animals of the first group (n=36) were housed in cages supplied with a running wheel, while mice of the second group (n=37) were housed in standard cages for control. Using a closed femur fracture model, bone repair was analysed by histomorphometry and biomechanical testing at 2 and 5 weeks. At 2 weeks, we additionally evaluated the expression of the proliferation marker PCNA (proliferating cell nuclear antigen) and the angiogenic and osteogenic growth factor VEGF (vascular endothelial growth factor). To standardise the mechanical conditions in the fracture gap, we used an intramedullary compression screw for stable fracture fixation. RESULTS Each mouse of the exercise group run a mean total distance of 23.5 km after 2 weeks and 104.3 km after 5 weeks. Histomorphometric analysis of the size and tissue composition of the callus could not reveal significant differences between mice undergoing exercise and controls. Accordingly, biomechanical testing showed a comparable torsional stiffness, peak rotation angle, and load at failure of the healing bones in the two groups. The expression of PCNA and VEGF did also not differ between mice of the exercise group and controls. CONCLUSION We conclude that increased exercise does not affect bone repair after stable fracture fixation.
Collapse
Affiliation(s)
- J H Holstein
- Department of Trauma, Hand & Reconstructive Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
48
|
Osmanbeyoglu HU, Hartmaier RJ, Oesterreich S, Lu X. Improving ChIP-seq peak-calling for functional co-regulator binding by integrating multiple sources of biological information. BMC Genomics 2012; 13 Suppl 1:S1. [PMID: 22369349 PMCID: PMC3439677 DOI: 10.1186/1471-2164-13-s1-s1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) is increasingly being applied to study genome-wide binding sites of transcription factors. There is an increasing interest in understanding the mechanism of action of co-regulator proteins, which do not bind DNA directly, but exert their effects by binding to transcription factors such as the estrogen receptor (ER). However, due to the nature of detecting indirect protein-DNA interaction, ChIP-seq signals from co-regulators can be relatively weak and thus biologically meaningful interactions remain difficult to identify. RESULTS In this study, we investigated and compared different statistical and machine learning approaches including unsupervised, supervised, and semi-supervised classification (self-training) approaches to integrate multiple types of genomic and transcriptomic information derived from our experiments and public database to overcome difficulty of identifying functional DNA binding sites of the co-regulator SRC-1 in the context of estrogen response. Our results indicate that supervised learning with naïve Bayes algorithm significantly enhances peak calling of weak ChIP-seq signals and outperforms other machine learning algorithms. Our integrative approach revealed many potential ERα/SRC-1 DNA binding sites that would otherwise be missed by conventional peak calling algorithms with default settings. CONCLUSIONS Our results indicate that a supervised classification approach enables one to utilize limited amounts of prior knowledge together with multiple types of biological data to enhance the sensitivity and specificity of the identification of DNA binding sites from co-regulator proteins.
Collapse
Affiliation(s)
- Hatice Ulku Osmanbeyoglu
- Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | | | | |
Collapse
|
|
49
|
Prisby R, Guignandon A, Vanden-Bossche A, Mac-Way F, Linossier MT, Thomas M, Laroche N, Malaval L, Langer M, Peter ZA, Peyrin F, Vico L, Lafage-Proust MH. Intermittent PTH(1-84) is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone-forming sites. J Bone Miner Res 2011; 26:2583-96. [PMID: 21713994 DOI: 10.1002/jbmr.459] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Intermittent parathyroid hormone (PTH) is anabolic for bone. Our aims were to determine (1) whether PTH stimulates bone angiogenesis and (2) whether vascular endothelial growth factor (VEGF A) mediates PTH-induced bone accrual. Male Wistar rats were given PTH(1-84) daily, and trabecular bone mass increased 150% and 92% after 30 and 15 days, respectively. The vascular system was contrasted to image and quantify bone vessels with synchrotron radiation microtomography and histology. Surprisingly, bone vessel number was reduced by approximately 25% and approximately 40% on days 30 and 15, respectively. PTH redistributed the smaller vessels closer to bone-formation sites. VEGF A mRNA expression in bone was increased 2 and 6 hours after a single dose of PTH and returned to baseline by 24 hours. Moreover, anti-VEGF antibody administration (1) blunted the PTH-induced increase in bone mass and remodeling parameters, (2) prevented the relocation of bone vessels closer to bone-forming sites, and (3) inhibited the PTH-induced increase in mRNA of neuropilin 1 and 2, two VEGF coreceptors associated with vascular development and function. In conclusion, PTH(1-84) is osteoanabolic through VEGF-related mechanism(s). Further, PTH spatially relocates blood vessels closer to sites of new bone formation, which may provide a microenvironment favorable for growth.
Collapse
Affiliation(s)
- Rhonda Prisby
- Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas 76019, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Holstein JH, Becker SC, Fiedler M, Scheuer C, Garcia P, Histing T, Klein M, Pohlemann T, Menger MD. Exercise enhances angiogenesis during bone defect healing in mice. J Orthop Res 2011; 29:1086-92. [PMID: 21259340 DOI: 10.1002/jor.21352] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2010] [Accepted: 12/13/2010] [Indexed: 02/04/2023]
Abstract
The aim of the present study was to investigate the effect of exercise on angiogenesis during bone defect healing in mice. We evaluated angiogenesis during cranial bone defect healing by intravital fluorescence microscopy (IVM) at days 0-21. To characterize the type of bone repair, we performed additional histomorphometric analyses at days 3-15. IVM was conducted in mice, which were housed in cages supplied with running wheels (exercise group; n=7) and compared to IVM results of mice, which were housed in cages without running wheels (controls; n=7). In the exercise group, we additionally performed correlation analyses between results of the IVM and the running distance. IVM showed an accelerated decrease of bone defect area in the exercise group compared to the control group. This was associated with a significantly higher blood vessel diameter in animals undergoing exercise at days 9 and 12 and a significant correlation between running distance and blood vessel density at day 9 (r = 0.74). Histomorphometry showed osseous bridging of the defect at day 9. The newly woven bone was covered by a neo-periosteum containing those blood vessels, which were visible by IVM. We conclude that exercise accelerates bone defect healing and stimulates angiogenesis during bore repair.
Collapse
Affiliation(s)
- Joerg H Holstein
- Department of Trauma, Hand and Reconstructive Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
| | | | | | | | | | | | | | | | | |
Collapse
|