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The Chronic multifocal osteomyelitis (CMO) mouse model develops IL-1\u03b2-driven sterile bone lesions reminiscent of severe CRMO. The goal of this study was to evaluate the potential involvement of mast cells in CMO\/CRMO. Here, we show that mast cells accumulate in inflamed tissues from CMO mice and that mast cell protease Mcpt1 can be detected in the peripheral blood. A transgenic model of connective tissue mast cell depletion (Mcpt5-Cre:Rosa26-Stopfl\/fl-DTa) was crossed with CMO mice and the resulting mice (referred to as CMO\/MC\u2013) showed a significant delay in disease onset compared with age-matched CMO mice. At 5-6\u2005months of age, CMO\/MC\u2013 mice had fewer bone lesions and immune infiltration in the popliteal lymph nodes that drain the affected tissues. In bone marrow-derived mast cell cultures from CMO mice, cytokine production in response to the alarmin IL-33 was elevated compared with wild-type cultures. To test the relevance of mast cells to human CRMO, we tested serum samples from a cohort of healthy controls and from CRMO patients at diagnosis. Interestingly, mast cell chymase was elevated in CRMO patients as well as in patients with oligoarticular juvenile arthritis. Tryptase-positive mast cells were also detected in bone lesions from CRMO patients and patients with bacterial osteomyelitis. Together, our results identify mast cells as cellular contributors to bone inflammation in CMO\/CRMO and provide rationale for further study of mast cells as therapeutic targets.<\/jats:p>","DOI":"10.1242\/dmm.040097","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T11:45:15Z","timestamp":1565005515000},"source":"Crossref","is-referenced-by-count":17,"title":["Mast cells enhance sterile inflammation in chronic nonbacterial osteomyelitis"],"prefix":"10.1242","volume":"12","author":[{"given":"Stephanie","family":"Young","sequence":"first","affiliation":[{"name":"Queen's University 1 Department of Biomedical and Molecular Sciences , , Kingston, ON K7L 3N6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namit","family":"Sharma","sequence":"additional","affiliation":[{"name":"Queen's University 1 Department of Biomedical and Molecular Sciences , , Kingston, ON K7L 3N6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Queen's University 1 Department of Biomedical and Molecular Sciences , , Kingston, ON K7L 3N6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Chitu","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine 2 Department of Developmental and Molecular Biology , , Bronx, NY 10461 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Neumeister","sequence":"additional","affiliation":[{"name":"University Hospital Carl Gustav Carus, Technical University Dresden 3 Departments of Clinical Chemistry and Laboratory Medicine , , Dresden 01307 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Sohr","sequence":"additional","affiliation":[{"name":"Children's Hospital Dresden, Technical University Dresden 4 Pediatric Rheumatology and Immunology , , Dresden 01307 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Richard","family":"Stanley","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine 2 Department of Developmental and Molecular Biology , , Bronx, NY 10461 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1295-6179","authenticated-orcid":false,"given":"Christian M.","family":"Hedrich","sequence":"additional","affiliation":[{"name":"Children's Hospital Dresden, Technical University Dresden 4 Pediatric Rheumatology and Immunology , , Dresden 01307 , Germany"},{"name":"Institute of Translational Medicine, University of Liverpool 5 Department of Women's & Children's Health , , Liverpool L14 5AB , UK"},{"name":"Alder Hey Children's NHS Foundation Trust Hospital 6 Department of Paediatric Rheumatology , , Liverpool L14 5AB , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2039-2393","authenticated-orcid":false,"given":"Andrew W. 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