Inhibition of articular cartilage degeneration by atorvastatin calcium via STAT1-caspase-3 signaling axis in rats with knee osteoarthritis

doi:10.12092/j.issn.1009-2501.2018.07.004

Abstract

Abstract:

AIM: To investigate the effect of atorvastatin calcium on the expression of STAT1, caspase-3 and on degeneration of articular cartilage in the knee osteoarthritis (KOA) rats. METHODS: SD rats were randomly divided into normal control group, model group and atorvastatin calcium treatment group. KOA rat model was established by Hulth method. After 8 weeks of experiment, the expression of TNF-α and IL-1β in serum of rats were detected by ELISA, X-ray examination was used to detect knee joint, articular cartilage HE staining were used for pathological observation, cartilage tissue p-STAT1 and cleaved caspase-3 protein expression levels were observed by immunohistochemistry and western blot.RESULTS:The levels of serum TNF-α and IL-1β in model group were significantly higher than those in normal group (P<0.01), while those in atorvastatin calcium group were lower than those in model group (P<0.01). Compared with the model group, the X-ray findings of atorvastatin calcium treatment group showed improvement of knee joint space, articular cartilage destruction and osteophyte formation. Atorvastatin calcium could significantly reduce the pathological changes of knee joint. Compared with model group, Mankin's score of articular cartilage in atorvastatin calcium treatment group decreased significantly (P<0.01). The expression of p-STAT1 and cleaved caspase-3 protein in articular cartilage of model group was significantly higher than that of normal group (P<0.01), while that of atorvastatin calcium group was lower than that of model group (P<0.01), and the correlation analysis showed that there was a linear positive correlation between p-STAT1 and cleaved caspase-3 (r=0.986, P<0.01).CONCLUSION:Atorvastatin inhibits the inflammation of the knee joint via STAT1-caspase-3 signal axis, thereby improving the degeneration of KOA articular cartilage.

Key words: knee osteoarthritis, atorvastatin calcium, STAT1-caspase-3 signaling axis, inflammatory cytokines

CLC Number:

R965.2

HUANG Lijia, HUANG Yang, KONG Jinsong, ZHENG Xin, GONG Xiaokang, RUAN Jianwei, WANG Haibao. Inhibition of articular cartilage degeneration by atorvastatin calcium via STAT1-caspase-3 signaling axis in rats with knee osteoarthritis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 743-748.

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