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The Role of Mast Cells in Bone Metabolism and Bone Disorders

Ragipoglu D1, Dudeck A2, Haffner-Luntzer M1, Voss M2, Kroner J1, Ignatius A1, Fischer V1.

Front Immunol. 2020 Feb 7;11:163. doi: 10.3389/fimmu.2020.00163. eCollection 2020.

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.

CONCLUSION The important role of MCs in allergic reactions has been known for several decades. However, the involvement of MCs in physiological bone turnover and bone disorders has been described only recently in more detail. As reviewed here, MCs secrete several mediators that are known to regulate bone formation and resorption, including histamine, IL-6, and TNF. Experimental data on the role of MCs in physiological bone turnover are contradictory and depend on the mouse model used. However, the involvement of MCs in various pathological skeletal conditions is clear, particularly in osteoporosis and RA. MCs may also regulate the fracture healing process by influencing the inflammatory response, angiogenesis, bone formation, and osteoclastogenesis (Figure 1). Osteoclastogenesis might be mainly, but not solely, regulated by MC-derived histamine. Further mechanistic investigations are required to elucidate MC functions in physiological and pathological conditions in bone. In consequence of the involvement of MCs in bone disorders, MC targeting drugs such as histamine H1 receptor blockers should be further tested for their therapeutic potential to treat osteoporosis, inflammatory bone disorders or disturbed bone repair.