高脂暴露可激活JAK2/STAT3信号通路而促进髓核细胞凋亡OA

Objective:Intervertebral disc degeneration(IDD)has been associated with low back pain,which is the leading cause of disability.Obesity has become a risk factor for IDD development.Obesity-associated IDD might be related to excessive mechanical loading,inflammation,and metabolic disorders.The underlying mechanism of obesity in promoting the pathogenesis of IDD is still unclear.Obesity has been associated with the activation of the JAK/STAT signaling pathway.This study aims to investigate whether obesity promoted IDD pathogenesis by activating the JAK2/STAT3 signaling pathway.Methods:High-fat diet(HFD)-induced rat obesity models were duplicated.Hematoxylin and eosin(HE)staining and immunohistochemistry(IHC)analysis were performed to study the pathological changes of cartilage.Palmitic acid(PA)was used to stimulate the nucleus pulposus(NP).Cell apoptosis was detected by a flow cytometer.Western blotting assays were used to determine the protein expression of Bax,Bcl-2,IL-6,JAK2,and STAT3.Results:In this study,it was found that an HFD could induce obesity and IDD development.In addition,high-fat exposure activated the JAK2/STAT3 signaling pathway and stimulated NP cell apoptosis.However,the JAK2 inhibitor Ruxolitinib could compromise the effects of PA on NP cell apoptosis.Conclusion:HFD-induced obesity may promote the pathogenesis of IDD by activating the JAK2/STAT3 signaling pathway.