title: The role of myofibroblasts in the development of osteoradionecrosis in a newly established rabbit model.
abstract: This study aimed to establish a proper animal model of osteoradionecrosis of jaws (ORNJ) and to observe preliminarily the characteristics of myofibroblasts, the key effector cell of fibrosis, in ORNJ. Rabbit mandibles were irradiated at three different doses based on a human equivalent radiation schedule, and examined by gross manifestation, single-photon emission computed tomography (SPECT), micro-computed tomography, sequential fluorochrome labeling, and histology. Immunohistochemistry staining of α-SMA was applied to detect the existence of myofibroblasts. The exposed necrotic bone, which is the main indication of ORNJ, started to be observed at all rabbits at 9 Gy. With the radiation dose increasing, the microarchitecture of the irradiated mandibles was more destroyed, the metabolism and mineralization of the irradiated mandibles diminished, the osteocytes number decreased, and more mature bones were substituted by fibrosis in the irradiated mandibles. In addition, as the radiation dose increased, the myofibroblast number increased and collected around the separated sequestrum, which indicated that myofibroblasts might relate to the pathogenesis of ORNJ. In summary, a clinically translational ORNJ model was successfully established in our study, and the role of myofibroblasts in the pathogenesis of ORNJ is described for the first time.
authors.affiliation: Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China; The State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zong
authors.affiliation: Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China; The State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Bolei
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Wen
authors.affiliation: National Health Service Lothian, West Lothian, United Kingdom.
authors.forename: Syed
authors.initials: S
authors.lastname: Alam
authors.affiliation: Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China; The State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China; The State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China; The State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yanpu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China; The State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China. Electronic address: tianleison@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008334:Mandible / Q000000981:diagnostic imaging / Q000473:pathology / Q000528:radiation effects; D008336:Mandibular Diseases / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D058628:Myofibroblasts / Q000502:physiology* / Q000528:radiation effects; D010025:Osteoradionecrosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D011817:Rabbits; D015899:Tomography, Emission-Computed, Single-Photon; D055114:X-Ray Microtomography
keywords: Animal model; Human equivalent radiation; Myofibroblasts; Osteoradionecrosis of jaws; Radiation-induced fibrosis