Zong Chunlin, Cai Bolei, Wen Xinxin, Alam Syed, Chen Yuanli, Guo Yuxuan, Liu Yanpu, Tian Lei
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.
Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
J Craniomaxillofac Surg. 2016 Jun;44(6):725-33. doi: 10.1016/j.jcms.2016.03.002. Epub 2016 Mar 19.
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.
本研究旨在建立一种合适的颌骨放射性骨坏死（ORNJ）动物模型，并初步观察成肌纤维细胞（纤维化的关键效应细胞）在ORNJ中的特征。根据人体等效辐射方案，对兔下颌骨进行三种不同剂量的照射，并通过大体表现、单光子发射计算机断层扫描（SPECT）、显微计算机断层扫描、连续荧光染料标记和组织学进行检查。应用α-SMA免疫组织化学染色检测成肌纤维细胞的存在。暴露的坏死骨是ORNJ的主要指征，在所有接受9 Gy照射的兔子中均开始观察到。随着辐射剂量的增加，照射后下颌骨的微观结构破坏更严重，照射后下颌骨的代谢和矿化减弱，骨细胞数量减少，照射后下颌骨中更多的成熟骨被纤维化取代。此外，随着辐射剂量的增加，成肌纤维细胞数量增加并聚集在分离的死骨周围，这表明成肌纤维细胞可能与ORNJ的发病机制有关。总之，本研究成功建立了一种具有临床转化意义的ORNJ模型，并首次描述了成肌纤维细胞在ORNJ发病机制中的作用。
