title: Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development of Bisphosphonate-related Osteonecrosis of the Jaw.
abstract: Injury to the barrier tissue initiates a rapid distribution of myeloid immune cells from bone marrow, which guide sound wound healing. Bisphosphonates, a widely used anti-bone resorptive drug with minimal systemic side effects, have been linked to an abnormal wound healing in the oral barrier tissue leading to, in some cases, osteonecrosis of the jaw (ONJ). Here we report that the development of ONJ may involve abnormal phenotypic plasticity of Ly6G+/Gr1+ myeloid cells in the oral barrier tissue undergoing tooth extraction wound healing. A bolus intravenous zoledronate (ZOL) injection to female C57Bl/6 mice followed by maxillary first molar extraction resulted in the development of ONJ-like lesion during the second week of wound healing. The multiplex assay of dissociated oral barrier cells exhibited the secretion of cytokines and chemokines, which was significantly modulated in ZOL mice. Tooth extraction-induced distribution of Ly6G+/Gr1+ cells in the oral barrier tissue increased in ZOL mice at week 2. ONJ-like lesion in ZOL mice contained Ly6G+/Gr1+ cells with abnormal size and morphology as well as different flow cytometric staining intensity. When anti-Ly6G (Gr1) antibody was intraperitoneally injected for 5 days during the second week of tooth extraction, CD11b+GR1(hi) cells in bone marrow and Ly6G+ cells in the oral barrier tissue were depleted, and the development of ONJ-like lesion was significantly attenuated. This study suggests that local modulation of myeloid cell plasticity in the oral barrier tissue may provide the basis for pathogenesis and thus therapeutic as well as preventive strategy of ONJ.
authors: From the Department of Dental Implant Centre, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing 100050, China, Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, and.
authors: Yujie
authors: Y
authors: Sun
authors: Weintraub Center for Reconstructive Biotechnology, Division of Oral Medicine and Biology, UCLA School of Dentistry, Los Angeles, California 90095.
authors: Kawaljit
authors: K
authors: Kaur
authors: Weintraub Center for Reconstructive Biotechnology, Department of Periodontology, Asahi University School of Dentistry, Gifu, Japan 501-0296.
authors: Keiichi
authors: K
authors: Kanayama
authors: Weintraub Center for Reconstructive Biotechnology, Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan 814-0175.
authors: Kenzo
authors: K
authors: Morinaga
authors: Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, and Division of Oral Medicine and Biology, UCLA School of Dentistry, Los Angeles, California 90095.
authors: Sil
authors: S
authors: Park
authors: Weintraub Center for Reconstructive Biotechnology, Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California 90095.
authors: Akishige
authors: A
authors: Hokugo
authors: Weintraub Center for Reconstructive Biotechnology, Division of Oral Medicine and Biology, UCLA School of Dentistry, Los Angeles, California 90095, Department of Tumor Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland 61-866, and.
authors: Anna
authors: A
authors: Kozlowska
authors: Division of Molecular and Cellular Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095.
authors: William H
authors: WH
authors: McBride
authors: From the Department of Dental Implant Centre, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing 100050, China, lijun3021@aliyun.com.
authors: Jun
authors: J
authors: Li
authors: Weintraub Center for Reconstructive Biotechnology, Division of Oral Medicine and Biology, UCLA School of Dentistry, Los Angeles, California 90095, ajewett@dentistry.ucla.edu.
authors: Anahid
authors: A
authors: Jewett
authors: Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, and Division of Oral Medicine and Biology, UCLA School of Dentistry, Los Angeles, California 90095, inishimura@dentistry.ucla.edu.
authors: Ichiro
authors: I
authors: Nishimura
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D005260:Female; D051379:Mice; D009055:Mouth / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D014081:Tooth Extraction; D014945:Wound Healing / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; C480309:Ly6G antigen, mouse
keywords: bone; bone marrow; necrosis (necrotic death); neutrophil; wound healing