The Small Molecule Drug BNTA Alleviates Osteoarthritis Caused by High Cholesterol by Upregulating Insig1 / 中国生物化学与分子生物学报

ABSTRACT

Osteoarthritis (OA) is a common degenerative disease of the motor system with a high morbidity and disability rate. The pathogenesis of OA is not clear at present. Previous studies believe that the pathogenesis of OA is mainly related to trauma factors, while recent studies have shown that metabolic factors, including abnormal cholesterol metabolism, are also closely related to OA. The treatment of OA is mainly symptomatic treatment at the early stage and surgical treatment at the late stage, and there is no specific drug. Previously, BNTA, a small molecule drug with cartilage protective effects, has been shown to have a good effect on OA caused by trauma, but its effect on OA caused by high cholesterol remains unclear. In order to explore the therapeutic effect of BNTA on OA caused by high cholesterol and its mechanism, the OA model of rats was constructed by adopting high cholesterol diets, and paraffin sections of knee joints were taken for histological evaluation. Lipid accumulation in chondrocytes of rats was assessed by oil red O staining. The expression of genes and proteins related to anabolism, catabolism and cholesterol metabolism in chondrocytes was assessed by RT-qPCR, immunofluorescence and immunohistochemistry. The results showed that BNTA could alleviate OA pathological manifestations and improve the OARSI (Osteoarthritis Research Society International) score in the OA model of high cholesterol rats. In rat chondrocytes, BNTA can promote the expression of anabolism-related genes col2, sox9 and acan, inhibit the expression of catabolism-related genes mmp13 and adamts5, and improve the lipid accumulation caused by high cholesterol in rat chondrocytes. BNTA can up-regulate Insig1 expression in rat chondrocytes and the OA model of high cholesterol rats. This study confirmed that high cholesterol can aggravate OA in vivo and in vitro, and can increase lipid accumulation in rat chondrocytes. Taken together, BNTA can alleviate OA phenotypes induced by high cholesterol and improve abnormal lipid accumulation in chondrocytes, possibly by inhibiting cholesterol biosynthesis in cells by upregulating Insig1, thereby alleviating abnormal lipid accumulation.