Chen Yun, Zhao Bingjie, Zhu Yong, Zhao Huaqiang, Ma Chuan
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University Jinan, Shandong Province, China.
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Department of Pediatric dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University Nanjing, Jiangsu Province, China.
Am J Transl Res. 2019 May 15;11(5):2969-2982. eCollection 2019.
Angiogenesis has been reported participated in temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis is unclear, recent studies indicate that hypoxia is important in TMJ-OA. In order to induce osteoarthritis-like lesions in mandibular condyles, rats were sleep deprived experimentally. An increased number of blood vessels were observed in the rats' condyles of SD and SR group compared with controls. Protein and mRNA levels of related factors including VEGF, HIF-1 and Notch were investigated by means of immunohistochemical staining, western blot and real-time PCR, which were highly expressed in the TMJ-OA rats. Furthermore, Cell test was designed to study effects of hypoxia on condylar chondrocytes. We found the expression of VEGF, HIF-1 and Notch were significantly increased in hypoxia group, indicating that HIF-1-Notch-VEGF signaling pathway were activated by hypoxia. The inhibitors of HIF-1 and Notch could suppress the expression of HIF-1, VEGF, Notch, suggesting the HIF-1-VEGF-Notch signaling pathway were bidirectional. Together, hypoxia played an important role in TMJ-OA and accelerates angiogenesis of condylar cartilage through HIF-1-VEGF-Notch signaling pathway. HIF-1α and Notch might be novel therapeutic targets in TMJ-OA.
已有报道称血管生成参与颞下颌关节骨关节炎（TMJ - OA）。虽然其发病机制尚不清楚，但最近的研究表明缺氧在TMJ - OA中起重要作用。为了在大鼠下颌髁突诱导出骨关节炎样病变，对大鼠进行实验性睡眠剥夺。与对照组相比，在SD组和SR组大鼠的髁突中观察到血管数量增加。通过免疫组织化学染色、蛋白质印迹和实时PCR研究了包括VEGF、HIF - 1和Notch在内的相关因子的蛋白质和mRNA水平，这些因子在TMJ - OA大鼠中高表达。此外，设计细胞试验以研究缺氧对髁突软骨细胞的影响。我们发现缺氧组中VEGF、HIF - 1和Notch的表达显著增加，表明HIF - 1 - Notch - VEGF信号通路被缺氧激活。HIF - 1和Notch的抑制剂可抑制HIF - 1、VEGF、Notch的表达，提示HIF - 1 - VEGF - Notch信号通路是双向的。总之，缺氧在TMJ - OA中起重要作用，并通过HIF - 1 - VEGF - Notch信号通路加速髁突软骨的血管生成。HIF - 1α和Notch可能是TMJ - OA新的治疗靶点。
