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1
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Wynn L, Hodges V, Criswell S. Mast Cell Concentrations in Pancreatic Disease Processes. Appl Immunohistochem Mol Morphol 2024; 32:163-168. [PMID: 37982564 DOI: 10.1097/pai.0000000000001174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 10/18/2023] [Indexed: 11/21/2023]
Abstract
Mast cells enumeration has been performed using various histologic staining techniques with the goal of elucidating the influence mast cells exert on pathologic processes. In this study, 77 human pancreatic tissues evidencing morphologically normal pancreas, benign fibrotic changes, endocrine tumors, and adenocarcinoma were evaluated using Wright stain and immunohistochemistry markers for tryptase and CD117. Mast cell counts were similar with tryptase and CD117 but were both significantly higher than counts obtained with the Wright stain. Furthermore, all analyses demonstrated that endocrine tumors and morphologically normal pancreatic tissues had significantly lower mast cell counts as compared with benign fibrosis and adenocarcinoma suggesting that the highly fibrotic nature of both pancreatitis and adenocarcinoma are related to increased mast cell concentrations.
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Affiliation(s)
- Lindsey Wynn
- Department of Diagnostic and Health Sciences, University of Tennessee Health Science Center
| | - Victoria Hodges
- Department of Pathology, Methodist University Hospital, Memphis, TN
| | - Sheila Criswell
- Department of Diagnostic and Health Sciences, University of Tennessee Health Science Center
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2
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Fischer V, Bülow JM, Krüger BT, Ragipoglu D, Vikman A, Haffner-Luntzer M, Katsoulis-Dimitriou K, Dudeck A, Ignatius A. Role of Mast-Cell-Derived RANKL in Ovariectomy-Induced Bone Loss in Mice. Int J Mol Sci 2023; 24:ijms24119135. [PMID: 37298085 DOI: 10.3390/ijms24119135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/17/2023] [Accepted: 05/20/2023] [Indexed: 06/12/2023] Open
Abstract
Mast cells may contribute to osteoporosis development, because patients with age-related or post-menopausal osteoporosis exhibit more mast cells in the bone marrow, and mastocytosis patients frequently suffer from osteopenia. We previously showed that mast cells crucially regulated osteoclastogenesis and bone loss in ovariectomized, estrogen-depleted mice in a preclinical model for post-menopausal osteoporosis and found that granular mast cell mediators were responsible for these estrogen-dependent effects. However, the role of the key regulator of osteoclastogenesis, namely, receptor activator of NFκB ligand (RANKL), which is secreted by mast cells, in osteoporosis development has, to date, not been defined. Here, we investigated whether mast-cell-derived RANKL participates in ovariectomy (OVX)-induced bone loss by using female mice with a conditional Rankl deletion. We found that this deletion in mast cells did not influence physiological bone turnover and failed to protect against OVX-induced bone resorption in vivo, although we demonstrated that RANKL secretion was significantly reduced in estrogen-treated mast cell cultures. Furthermore, Rankl deletion in mast cells did not influence the immune phenotype in non-ovariectomized or ovariectomized mice. Therefore, other osteoclastogenic factors released by mast cells might be responsible for the onset of OVX-induced bone loss.
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Affiliation(s)
- Verena Fischer
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany
| | - Jasmin Maria Bülow
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany
| | - Benjamin Thilo Krüger
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany
| | - Deniz Ragipoglu
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany
| | - Anna Vikman
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany
| | - Melanie Haffner-Luntzer
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany
| | - Konstantinos Katsoulis-Dimitriou
- Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Anne Dudeck
- Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
- Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany
| | - Anita Ignatius
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, 89081 Ulm, Germany
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Does anti-IgE therapy prevent chronic allergic asthma-related bone deterioration in asthmatic mice? J Biomech 2022; 141:111180. [PMID: 35724549 DOI: 10.1016/j.jbiomech.2022.111180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/06/2022] [Accepted: 06/06/2022] [Indexed: 11/21/2022]
Abstract
Current evidence on the association between allergic diseases and bone metabolism indicates asthma may be a potential risk factor for bone health. Using anti-IgE has been proven effective in allergic asthma treatment with a good safety profile; however, its effects on bone health are unknown. Thus, we aimed to investigate whether: (i) chronic allergic asthma (CAA) causes any meaningful changes in bone, and if any, (ii) anti-IgE therapy prevents any CAA-induced adverse alteration. A murine model was used to study CAA. Thirty-two BALB/c male-mice were assigned into four groups (eight-mice/group): Control, CAA (treated with saline), CAA + 100 µg of anti-IgE (CAA + 100AIgE), and CAA + 200 µg of anti-IgE (CAA + 200AIgE) groups. After immunization, saline or anti-IgE was performed intraperitoneally for 8-weeks (in five-sessions at 15-days interval). Three-point bending test was used for the mechanical analysis. Bone calcium (Ca2+) and phosphorus (P3-) as well as Ca/P ratio were evaluated using inductively-coupled plasma-mass-spectrometer (ICP-MS). Compared to control, reductions observed in yield and ultimate moments, rigidity, energy-to-failure, yield and ultimate stresses, elastic modulus, toughness, and post-yield toughness parameters of the CAA group were found significant (P < 0.05). Similar declines were also detected regarding bone Ca2+, P3- and Ca/P ratio (P < 0.05). Compared to control, we observed that 200 µg administration of anti-IgE in CAA + 200AIgE group hindered CAA-related impairments in mineral and mechanical characteristics of bone, while 100 µg in CAA + 100AIgE failed to do so. Our results showed CAA may cause bone loss, leading to a decrease in bone strength, and anti-IgE administration may dose-dependently inhibit these impairments in bone.
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Fischer V, Ragipoglu D, Diedrich J, Steppe L, Dudeck A, Schütze K, Kalbitz M, Gebhard F, Haffner-Luntzer M, Ignatius A. Mast Cells Trigger Disturbed Bone Healing in Osteoporotic Mice. J Bone Miner Res 2022; 37:137-151. [PMID: 34633111 DOI: 10.1002/jbmr.4455] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 09/21/2021] [Accepted: 10/03/2021] [Indexed: 12/16/2022]
Abstract
Mast cells are important tissue-resident sensor and effector immune cells but also play a major role in osteoporosis development. Mast cells are increased in numbers in the bone marrow of postmenopausal osteoporotic patients, and mast cell-deficient mice are protected from ovariectomy (OVX)-induced bone loss. In this study, we showed that mast cell-deficient Mcpt5-Cre R-DTA mice were protected from OVX-induced disturbed fracture healing, indicating a critical role for mast cells in the pathomechanisms of impaired bone repair under estrogen-deficient conditions. We revealed that mast cells trigger the fracture-induced inflammatory response by releasing inflammatory mediators, including interleukin-6, midkine (Mdk), and C-X-C motif chemokine ligand 10 (CXCL10), and promote neutrophil infiltration into the fracture site in OVX mice. Furthermore, mast cells were responsible for reduced osteoblast and increased osteoclast activities in OVX mice callus, as well as increased receptor activator of NF-κB ligand serum levels in OVX mice. Additional in vitro studies with human cells showed that mast cells stimulate osteoclastogenesis by releasing the osteoclastogenic mediators Mdk and CXCL10 in an estrogen-dependent manner, which was mediated via the estrogen receptor alpha on mast cells. In conclusion, mast cells negatively affect the healing of bone fractures under estrogen-deficient conditions. Hence, targeting mast cells might provide a therapeutic strategy to improve disturbed bone repair in postmenopausal osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Verena Fischer
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
| | - Deniz Ragipoglu
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
| | - Johanna Diedrich
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
| | - Lena Steppe
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
| | - Anne Dudeck
- Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Konrad Schütze
- Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, University Medical Center Ulm, Ulm, Germany
| | - Miriam Kalbitz
- Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, University Medical Center Ulm, Ulm, Germany.,Department of Trauma and Orthopedic Surgery, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen-Nürnberg, Germany
| | - Florian Gebhard
- Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, University Medical Center Ulm, Ulm, Germany
| | - Melanie Haffner-Luntzer
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
| | - Anita Ignatius
- Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany
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Ehnert S, Relja B, Schmidt-Bleek K, Fischer V, Ignatius A, Linnemann C, Rinderknecht H, Huber-Lang M, Kalbitz M, Histing T, Nussler AK. Effects of immune cells on mesenchymal stem cells during fracture healing. World J Stem Cells 2021; 13:1667-1695. [PMID: 34909117 PMCID: PMC8641016 DOI: 10.4252/wjsc.v13.i11.1667] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/31/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
In vertebrates, bone is considered an osteoimmune system which encompasses functions of a locomotive organ, a mineral reservoir, a hormonal organ, a stem cell pool and a cradle for immune cells. This osteoimmune system is based on cooperatively acting bone and immune cells, cohabitating within the bone marrow. They are highly interdependent, a fact that is confounded by shared progenitors, mediators, and signaling pathways. Successful fracture healing requires the participation of all the precursors, immune and bone cells found in the osteoimmune system. Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing. In this review, first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely. The separate paragraphs focus on the specific cell types, starting with the cells of the innate immune response followed by cells of the adaptive immune response, and the complement system as mediator between them. Finally, a brief overview on the challenges of preclinical testing of immune-based therapeutic strategies to support fracture healing will be given.
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Affiliation(s)
- Sabrina Ehnert
- Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Tübingen 72076, Germany
| | - Borna Relja
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke University, Magdeburg 39120, Germany
| | - Katharina Schmidt-Bleek
- Julius Wolff Institute and Berlin Institute of Health Center of Regenerative Therapies, Charité - University Medicine Berlin, Berlin 13353, Germany
| | - Verena Fischer
- Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm 89091, Germany
| | - Anita Ignatius
- Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm 89091, Germany
| | - Caren Linnemann
- Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Tübingen 72076, Germany
| | - Helen Rinderknecht
- Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Tübingen 72076, Germany
| | - Markus Huber-Lang
- Institute for Clinical and Experimental Trauma-Immunology (ITI), University Hospital Ulm, Ulm 89091, Germany
| | - Miriam Kalbitz
- Department of Trauma and Orthopedic Surgery, University Hospital Erlangen Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen 91054, Germany
| | - Tina Histing
- Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Tübingen 72076, Germany
| | - Andreas K Nussler
- Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Tübingen 72076, Germany
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Saxena Y, Routh S, Mukhopadhaya A. Immunoporosis: Role of Innate Immune Cells in Osteoporosis. Front Immunol 2021; 12:687037. [PMID: 34421899 PMCID: PMC8374941 DOI: 10.3389/fimmu.2021.687037] [Citation(s) in RCA: 103] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 07/22/2021] [Indexed: 12/11/2022] Open
Abstract
Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as 'bone remodeling'. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term "immunoporosis" to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.
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Affiliation(s)
- Yogesh Saxena
- Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India
| | - Sanjeev Routh
- Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India
| | - Arunika Mukhopadhaya
- Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, India
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Leone A, Criscuolo M, Gullì C, Petrosino A, Carlo Bianco N, Colosimo C. Systemic mastocytosis revisited with an emphasis on skeletal manifestations. Radiol Med 2020; 126:585-598. [PMID: 33242205 DOI: 10.1007/s11547-020-01306-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 11/15/2020] [Indexed: 12/12/2022]
Abstract
Systemic mastocytosis (SM) is a rare form of mastocytosis that can affect various organ systems. Bone involvement is the most common and prominent imaging feature in patients with SM regardless of the subtype. Furthermore, bone involvement is a prognostic factor as it may entail an aggressive course of the disease. Diagnosis is established by bone marrow biopsy complemented by imaging modalities such as radiography, CT, and magnetic resonance (MR) imaging. The radiographic and CT appearances are that of sclerotic, lytic, or mixed patterns with focal or diffuse distribution, involving primarily the axial skeleton and the ends of the long bones. Bone marrow infiltration is best recognized on MR imaging. Osteoporosis is common in SM; thus, a bone mineral density measurement at lumbar spine and proximal femur by dual-energy X-ray absorptiometry should be obtained. Imaging plays a huge part in the diagnostic process; when skeletal imaging findings are carefully interpreted and correlated with clinical features, they can lead to the suspicion of SM. The primary aims of this review article were to focus on the role of imaging in detection and characterization of skeletal patterns of SM and to discuss relevant clinical features that could facilitate prompt and correct diagnosis.
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Affiliation(s)
- Antonio Leone
- Department of Radiological and Hematological Sciences Fondazione, Policlinico Universitario A. Gemelli, IRCCS Università Cattolica del Sacro Cuore, Largo A. Gemelli, 100168, Rome, Italy.
| | - Marianna Criscuolo
- Department of Radiological and Hematological Sciences Fondazione, Policlinico Universitario A. Gemelli, IRCCS Università Cattolica del Sacro Cuore, Largo A. Gemelli, 100168, Rome, Italy
| | - Consolato Gullì
- Department of Radiological and Hematological Sciences Fondazione, Policlinico Universitario A. Gemelli, IRCCS Università Cattolica del Sacro Cuore, Largo A. Gemelli, 100168, Rome, Italy
| | - Antonella Petrosino
- Department of Radiological and Hematological Sciences Fondazione, Policlinico Universitario A. Gemelli, IRCCS Università Cattolica del Sacro Cuore, Largo A. Gemelli, 100168, Rome, Italy
| | - Nicola Carlo Bianco
- Department of Radiological and Hematological Sciences Fondazione, Policlinico Universitario A. Gemelli, IRCCS Università Cattolica del Sacro Cuore, Largo A. Gemelli, 100168, Rome, Italy
| | - Cesare Colosimo
- Department of Radiological and Hematological Sciences Fondazione, Policlinico Universitario A. Gemelli, IRCCS Università Cattolica del Sacro Cuore, Largo A. Gemelli, 100168, Rome, Italy
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Ragipoglu D, Dudeck A, Haffner-Luntzer M, Voss M, Kroner J, Ignatius A, Fischer V. The Role of Mast Cells in Bone Metabolism and Bone Disorders. Front Immunol 2020; 11:163. [PMID: 32117297 PMCID: PMC7025484 DOI: 10.3389/fimmu.2020.00163] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 01/21/2020] [Indexed: 12/15/2022] Open
Abstract
Mast cells (MCs) are important sensor and effector cells of the immune system that are involved in many physiological and pathological conditions. Increasing evidence suggests that they also play an important role in bone metabolism and bone disorders. MCs are located in the bone marrow and secrete a wide spectrum of mediators, which can be rapidly released upon activation of mature MCs following their differentiation in mucosal or connective tissues. Many of these mediators can exert osteocatabolic effects by promoting osteoclast formation [e.g., histamine, tumor necrosis factor (TNF), interleukin-6 (IL-6)] and/or by inhibiting osteoblast activity (e.g., IL-1, TNF). By contrast, MCs could potentially act in an osteoprotective manner by stimulating osteoblasts (e.g., transforming growth factor-β) or reducing osteoclastogenesis (e.g., IL-12, interferon-γ). Experimental studies investigating MC functions in physiological bone turnover using MC-deficient mouse lines give contradictory results, reporting delayed or increased bone turnover or no influence depending on the mouse model used. By contrast, the involvement of MCs in various pathological conditions affecting bone is evident. MCs may contribute to the pathogenesis of primary and secondary osteoporosis as well as inflammatory disorders, including rheumatoid arthritis and osteoarthritis, because increased numbers of MCs were found in patients suffering from these diseases. The clinical observations could be largely confirmed in experimental studies using MC-deficient mouse models, which also provide mechanistic insights. MCs also regulate bone healing after fracture by influencing the inflammatory response toward the fracture, vascularization, bone formation, and callus remodeling by osteoclasts. This review summarizes the current view and understanding of the role of MCs on bone in both physiological and pathological conditions.
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Affiliation(s)
- Deniz Ragipoglu
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Anne Dudeck
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Melanie Haffner-Luntzer
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Martin Voss
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Jochen Kroner
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Anita Ignatius
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
| | - Verena Fischer
- Trauma Research Center Ulm, Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany
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9
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Zinc inhibits ovariectomy induced microarchitectural changes in the bone tissue. JOURNAL OF NUTRITION & INTERMEDIARY METABOLISM 2016. [DOI: 10.1016/j.jnim.2015.12.333] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Sánchez-Muñoz L, Teodósio C, Morgado JM, Escribano L. Immunophenotypic Characterization of Bone Marrow Mast Cells in Mastocytosis and Other Mast Cell Disorders. Methods Cell Biol 2011; 103:333-59. [DOI: 10.1016/b978-0-12-385493-3.00014-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Escribano L, Navalón R, Núñez R, Díaz Agustín B, Bravo P. Immunophenotypic analysis of human mast cells by flow cytometry. ACTA ACUST UNITED AC 2008; Chapter 6:Unit 6.6. [PMID: 18770717 DOI: 10.1002/0471142956.cy0606s12] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The immunophenotypic identification and enumeration of human bone marrow mast cells represents a clear demonstration of the utility of flow cytometry for rare-event analysis. The basic approach can be applied to a variety of specimens, including bone marrow, peripheral blood, ascitic fluid, and lymphoid tissue such as adenoids. Special emphasis is placed on markers with potential utility for distinguishing between normal, reactive, and pathological mast cells. From the clinical aspect, immunophenotypic analysis of mast cells may have great utility in supporting the diagnosis of tissue involvement in mastocytosis.
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Affiliation(s)
- L Escribano
- Hospital Ramón y Cajal, Mast Cell Unit, Madrid, Spain
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12
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Abstract
Historically, mast cells were known as a key cell type involved in type I hypersensitivity. Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the ileum and colon of patients with IBD, which was accompanied by great changes of the content in mast cells such as dramatically increased expression of TNF-α, IL-16 and substance P. The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of patients with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD. However, little is known of the actions of histamine, tryptase, chymase and carboxypeptidase in IBD. Over the last decade, heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the patients showed good clinical and laboratory response with no serious adverse effects. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner. The hypothesis is that mast cell secretogogues induce mast cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H1 receptor. Whereas released tryptase acts similarly to histamine, but activates mast cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the pathogenesis of IBD. In conclusion, while pathogenesis of IBD remains unclear, the key role of mast cells in this group of diseases demonstrated in the current review implicates strongly that IBD is a mast cell associated disease. Therefore, close attentions should be paid to the role of mast cells in IBD.
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Affiliation(s)
- Shao-Heng He
- Allergy and Inflammation Research Institute, Medical College, Shantou University, Shantou 515031, Guangdong Province, China.
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Gorustovich A, de los Esposito M, Guglielmotti MB, Giglio MJ. Periimplant Bone Healing under Experimental Hepatic Osteodystrophy Induced by a Choline-Deficient Diet: A Histomorphometric Study in Rats. Clin Implant Dent Relat Res 2003; 5:124-9. [PMID: 14536047 DOI: 10.1111/j.1708-8208.2003.tb00193.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Osseointegration and success of an implant involve the interaction of local and systemic factors such as bone metabolic diseases. PURPOSE The purpose of this study was to evaluate the effect of experimental hepatic osteodystrophy induced by a choline-deficient diet on periimplant bone healing. MATERIALS AND METHODS Laminar titanium implants were placed in the tibias of five groups of Wistar rats: those with a (1). controlled diet for 15 days; (2). choline-deficient diet for 15 days; (3). controlled diet for 30 days; (4). choline-deficient diet for 30 days; (5). choline-deficient diet for 15 days and a controlled diet for 15 days (refeeding). Body weight and food intake, hematocrit, and hemoglobinemia were evaluated. The animals were killed at 15 or 30 days post implantation. The liver, kidneys, and tibias were resected and fixed in 20% formalin solution. The tibias were radiographed and processed for histomorphometric evaluation of the periimplant bone area. RESULTS Histologic studies revealed steatosis in the liver but no alterations in the kidneys. Rats fed a choline-deficient diet showed periimplant bone healing with marked qualitative and quantitative alterations. The periimplant bone area was 28% and 75% lower in experimental animals than in controls at 15 and 30 days, respectively. CONCLUSIONS Liver alterations caused by a choline-deficient diet alter periimplant osteogenesis qualitatively and quantitatively.
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Affiliation(s)
- Alejandro Gorustovich
- Department of Oral Pathology, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
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Brumsen C, Papapoulos SE, Lentjes EGWM, Kluin PM, Hamdy NAT. A potential role for the mast cell in the pathogenesis of idiopathic osteoporosis in men. Bone 2002; 31:556-61. [PMID: 12477568 DOI: 10.1016/s8756-3282(02)00875-x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Osteoporosis is increasingly being recognized in men. Secondary causes are often implicated, but the mechanism of bone loss remains unclear in about a third of patients. The mast cell is a complex cell that stores a number of factors known to affect bone metabolism. Patients with systemic mastocytosis often demonstrate osteoporosis and bone marrow mast cells may be increased in osteoporotic postmenopausal women. We address the possible role of the mast cell in the pathophysiology of male osteoporosis by studying the relationship between bone marrow infiltration with mast cells and the 24 h urine excretion of N-methylhistamine, and the severity of osteoporosis in 48 consecutive men with idiopathic osteoporosis (bone mineral density Z score of <-1 and/or at least one prevalent vertebral fracture). Secondary causes for osteoporosis were excluded and none of the patients had systemic manifestations of enhanced mast cell activity. A widely variable number of morphologically normal mast cells were counted in toluidine blue-stained sections from 42 of 46 evaluable bone marrow biopsies. In 4 of the 42 biopsies (9%), clusters of abnormal mast cells were identified. These four patients were the only ones who also demonstrated increased 24 h urine excretion of N-methylhistamine. There was a significant positive relationship between mast cell number and the 24 h urine excretion of N-methylhistamine reflecting mast cell activity (p = 0.0001), and this latter measurement correlated negatively with bone mineral density (BMD) at the lumbar spine (p < 0.001). We identified clinically important bone marrow cell infiltration with pathologic mast cells in the absence of systemic manifestations of mast cell hyperactivity as an additional secondary cause for osteoporosis in some 9% of men with idiopathic osteoporosis, and found urinary excretion of N-methylhistamine to be above the upper limit of the normal laboratory reference range diagnostic for this cause of secondary osteoporosis. The more continuous spectrum in the relationship between mast cell activity and BMD supports a potential role for this cell in the pathogenesis of idiopathic male osteoporosis.
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Affiliation(s)
- C Brumsen
- Endocrinology and Metabolic Diseases, Leiden, The Netherlands
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Abstract
Mastocytosis represents a heterogeneous group of clinical disorders resulting from the infiltration of mast cells in the skin and other organs. Although mastocytosis was first described over 130 years ago, the pathophysiologic mechanisms responsible for this disease have been identified only recently. This article discusses the salient clinical features of the disease, the mechanisms responsible for its development, and provides treatment approaches that have proven useful for managing patients with this disorder.
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Affiliation(s)
- M D Tharp
- Department of Dermatology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA
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Lesclous P, Guez D, Llorens A, Saffar JL. Time-course of mast cell accumulation in rat bone marrow after ovariectomy. Calcif Tissue Int 2001; 68:297-303. [PMID: 11683537 DOI: 10.1007/bf02390837] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
We previously reported that mast cells accumulate in the tibia bone marrow of ovariectomized (OVX) rats. In this study, the timing of mast cell accumulation and osteoclast generation were compared to determine whether or not mast cell accumulation preceded osteoclast recruitment after ovariectomy. This may be significant because of the number of cytokines released by mast cells that are potentially active on resorption. Sprague-Dawley rats (120) aged 12 weeks were OVX or sham-operated, and killed on days 4, 7, 14, 28, and 56 postsurgery. Ten additional intact rats were used as baseline controls. Ovariectomy was confirmed by a sharp and sustained fall in serum estradiol. The loss in trabecular bone volume (BV/TV) began on day 7, reaching 80% on day 56 (P < 0.001 vs baseline controls). The number of osteoclasts (N.OC/TBPm) increased in the OVX rats between days 4 and 7 (+130%; P < 0.001), and continued rising to day 28. During the next month, it decreased greatly (-63%, P < 0.001 on day 56 vs day 28). In the sham-treated rats, few mast cells were scattered in the bone marrow (1.9 cells/mm2 in the baseline controls). Their number fluctuated during the experimental period, but at each time-point it was lower than in the OVX rats. They were predominantly (90%) of the mucosal subtype. In the OVX rats, their number doubled between days 4 and 14 (P < 0.001), reached 8.6 cells/mm2 on day 28 (a 5.4-fold increase compared with day 4 OVX rats), and plateaued for the next 4 weeks. OVX had no effects on mast cell subtypes. In conclusion, mast cell accumulation and osteoclast differentiation are precocious and concomitant; this does not support a direct role for mast cells in osteoclast recruitment. Rather, the two cell populations may derive from a common precursor or be targeted simultaneously by estrogen depletion through common stimulator(s). Mast cell hyperplasia appears to be a significant, and usually unknown, manifestation of ovariectomy in the bone marrow environment.
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Affiliation(s)
- P Lesclous
- Laboratoire de Biologie et Physiopathologie Crânio-Faciales, Faculté de Chirurgie Dentaire Université René Descartes (Paris-V), Montrouge, France
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