Osteopontin accelerates chondrocyte proliferation in osteoarthritis rats through the NF-κb signaling pathway

摘要

OBJECTIVE: To explore the influence of osteopontin (OPN) on the chondrocyte proliferation in osteoarthritis (OA) rats. MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were divided in the control group (n=10), model group (n=10), and OPN knockdown group (n=10). No treatment was performed in the control group, while OA rats were administrated with control adenovirus in the model group and OPN knockdown adenovirus in the OPN knockdown group. After sampling, the degree of OA was evaluated via hematoxylin-eosin (HE) staining, and the mRNA expression of OPN was detected. Moreover, the expression of the proliferation-associated protein cyclin D1 was detected using immunohistochemistry. The chondrocytes were isolated from the normal rats, cultured, and transfected with OPN overexpression vector or si-OPN. Methyl thiazolyl tetrazolium (MTT) assay was adopted to determine the proliferative capacity of chondrocytes, and Caspase3 activity was measured to evaluate the changes in the apoptotic capacity of chondrocytes. Meanwhile, Western blotting was performed to verify the influences of OPN on the pathways on chondrocyte proliferation. RESULTS: After the OA model was established, the expression level of OPN significantly increased. According to HE staining results, OPN knockdown effectively inhibited the onset of OA. Compared with that in the control group, the expression level of cyclin D1 in the model group was raised. However, upregulated cyclin D1 in OA rats was repressed in OPN knockdown group. OPN overexpression promoted the proliferation of chondrocytes, but suppressed their apoptosis, while OPN knockdown had the opposite effects. Besides, OPN overexpression upregulated nuclear factor-κB (NF-κB), and NF-κB knockdown eliminated the regulatory effects of OPN on proliferation and apoptosis of chondrocytes. CONCLUSIONS: OPN promotes the expression of NF-κB signals to accelerate chondrocyte proliferation, thereby inducing OA in rats.