Effects Of HIF-1/Notch Signaling Pathway On Temporomandibular Joint Osteoarthritis

Objective:To evaluate the effects of HIF-1/Notch signaling pathway on the development of temporomandibular joint osteoarthritis (TMJ-OA).Methods:180 male 8-week-old Wistar rats were randomly divided into threesgroups:sleep deprivation (SD) group, spontaneous recovery (SR) group and the control (CN) group (n=60 per group). Each group of the three groups were then randomly divided into three subgroups (n=20 per subgroup) according to the time point that the rats were killed (4,6 and 8 weeks).The modified multiple platform method (MMPM) was used to induce experimentally TMJ-OA rat models. The pathological changes of TMJ condylar cartilage were observed by hematoxylin and eosin (HE) staining. The chondropathy was scored and osteochondral junction micro vessel density (MVD) was assessed by means of immunofluorescence using polyclonal antibodies against CD 105 (endoglin). The expression levels of HIF-1α、Notch-1、VEGF and Hes 1 were further investigated by means of immunohistochemisty, Western Blot and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses.Results:HE staining showed that condylar cartilages of the rats of CN groups displayed normal appearance, while histological changes were observed in SD and SR groups. The histological changes in SR groups were mild and relative uncommon compared with SD groups, and chondropathy scores of SD groups were significantly higher than that of SR groups and CN groups, showed progressive enhancement in a time-dependent manner.The osteochondral junction MVDs of SD and SR groups were significantly higher than that of CN groups; however, there was no statistical difference between them. MVDs of both SD and SR groups increased with time, and were closely related to chondropathy scores in SD groups, but no relevant in SR groups.Immunohistochemisty showed that positive staining of HIF-1α Notch-1、VEGF were uncommon in CN groups, while were concentrated in the chondrocytes of the deep layer and around the blood vessels in SD and SR groups. The immunoreactivities of HIF-1α Notch-1、VEGF were associated with chondropathy scores in both SD and SR groups, and were closely related to MVD in SD groups.Western Blot and RT-PCR indicated that the protein and mRNA expression levels of HIF-1α Notch-1、VEGF, and the mRNA expression levels of Hes 1 almost in the same manner. The expression levels were higher in that of SD groups than SR groups than CN groups, and increased in a time-dependent manner in both SD and SR groups What’s more, the mRNA expression levels of HIF-1α、Notch-1、VEGF and Hes 1 were closely related to each other.Conclusion:Sleep deprivation of rats through MMPM could induce TMJ-OA like histological changes, and showed progressive enhancement in a time-dependent manner.Angiogenesis of TMJ condylar cartilage was a crucial histological change of TMJ-OA, also involved in the occurrence and development of TMJ-OA caused by psychological factor (chronic sleep deprivation).HIF-1/Notch signaling pathway played an important role in angiogenesis of TMJ condylar cartilage, and also participated in the development and progression of TMJ-OA.