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Role of dendritic cell‐mediated immune response in oral homeostasis: A new mechanism of osteonecrosis of the jaw
Author(s) -
Elsayed Ranya,
Kurago Zoya,
Cutler Christopher W.,
Arce Roger M.,
Gerber Jennifer,
Celis Esteban,
Sultan Hussein,
Elashiry Mahmoud,
Meghil Mohamed,
Sun Christina,
Auersvald Caroline M.,
Awad Mohamed E.,
Zeitoun Rana,
Elsayed Riham,
Eldin M. Elshikh Mohey,
Isales Carlos,
Elsalanty Mohammed E.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901819rr
Subject(s) - immune system , osteonecrosis of the jaw , dendritic cell , acquired immune system , immunology , t cell , homeostasis , microbiology and biotechnology , medicine , cancer research , biology , osteoporosis , bisphosphonate
Dendritic cells are an important link between innate and adaptive immune response. 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‐related 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‐resident DCs, promoting disruption of T‐cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC‐deficient 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‐cell activation. We conclude that the mechanism of Zol‐induced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response.