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Mast Cells Are Critical Regulators of Bone Fracture–Induced Inflammation and Osteoclast Formation and Activity
Author(s) -
Kroner Jochen,
Kovtun Anna,
Kemmler Julia,
Messmann Joanna J,
Strauss Gudrun,
Seitz Sebastian,
Schinke Thorsten,
Amling Michael,
Kotrba Johanna,
Froebel Julia,
Dudeck Jan,
Dudeck Anne,
Ignatius Anita
Publication year - 2017
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3234
Subject(s) - osteoclast , inflammation , bone healing , bone remodeling , immune system , mast cell , osteoimmunology , histamine , microbiology and biotechnology , immunology , bone marrow , innate immune system , medicine , biology , chemistry , receptor , rankl , anatomy , activator (genetics)
Mast cells, important sensor and effector cells of the immune system, may influence bone metabolism as their number is increased in osteoporotic patients. They are also present during bone fracture healing with currently unknown functions. Using a novel c‐Kit ‐independent mouse model of mast cell deficiency, we demonstrated that mast cells did not affect physiological bone turnover. However, they triggered local and systemic inflammation after fracture by inducing release of inflammatory mediators and the recruitment of innate immune cells. In later healing stages, mast cells accumulated and regulated osteoclast activity to remodel the bony fracture callus. Furthermore, they were essential to induce osteoclast formation after ovariectomy. Additional in vitro studies revealed that they promote osteoclastogenesis via granular mediators, mainly histamine. In conclusion, mast cells are redundant in physiologic bone turnover but exert crucial functions after challenging the system, implicating mast cells as a potential target for treating inflammatory bone disorders. © 2017 American Society for Bone and Mineral Research.