HIF-1-VEGF-Notch mediates angiogenesis in temporomandibular joint osteoarthritis

American Journal of Translational Research

Bingjie Zhao¹  Yun Chen²  Yong Zhu³ 

[1]Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Department of Pediatric dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu Province, China

[2]Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, Shandong Province, China

[3]Xuanwu Leader Dental Clinic, Nanjing, China

关键词: TMJ-OA;    hypoxia;    angiogenesis;    HIF-1;    Notch;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

CC BY-NC