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The role of dendritic cells in bone homeostasis, however, is not understood. Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication\u2010related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol in impairment of differentiation and function of migratory and tissue\u2010resident DCs, promoting disruption of T\u2010cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC\u2010deficient mice were predisposed to osteonecrosis following dental extraction. Zol treatment of DCs in vitro caused an impairment in immune functions including differentiation, maturation, migration, antigen presentation, and T\u2010cell activation. We conclude that the mechanism of Zol\u2010induced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response.<\/jats:p>","DOI":"10.1096\/fj.201901819rr","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T02:03:38Z","timestamp":1578621818000},"page":"2595-2608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Role of dendritic cell\u2010mediated immune response in oral homeostasis: A new mechanism of osteonecrosis of the jaw"],"prefix":"10.1096","volume":"34","author":[{"given":"Ranya","family":"Elsayed","sequence":"first","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoya","family":"Kurago","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"},{"name":"Biochemistry and Molecular Biology Georgia Cancer Center Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Cutler","sequence":"additional","affiliation":[{"name":"Department of Periodontics Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger M.","family":"Arce","sequence":"additional","affiliation":[{"name":"Department of Periodontics Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gerber","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Celis","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Georgia Cancer Center Medical College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Sultan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology School of Medicine Washington University St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Elashiry","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"},{"name":"Department of Periodontics Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Meghil","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"},{"name":"Department of Periodontics Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Auersvald","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed E.","family":"Awad","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Zeitoun","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Diagnostic Sciences Dental College of Georgia Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riham","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohey","family":"Eldin M. 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