Simvastatin retards cartilage degradation and subchondral bone deterioration induced by a high-fat diet in mice

Abstract

ABSTRACTTo evaluate the effects of simvastatin on the degeneration of cartilage and subchondral bone in a mice model of osteoarthritis (OA) induced by obesity. Thirty male 3-month-old C57BL/6J mice were randomized into three groups: mice with normal diet + vehicle (distilled water) (Control), mice with High-fat diet + vehicle (HFD), mice with HFD + Simvastatin (HFD+S). HFD+S group were treated with simvastatin (10 mg/kg/day) for 12 weeks. The pathology of OA was assessed by histomorphology analyses, immunohistochemistry, micro-computed tomography, and enzyme-linked immunosorbent assay. Histomorphological analysis revealed that OA was significantly exacerbated by the HFD-induced obesity and markedly alleviated by the simvastatin intervention. In details, simvastatin ameliorated the abnormal metabolic status and cartilage lesions, significantly increased aggrecan and collagen-II expression and decreased the expression of MMP-13 and leptin in cartilage. Furthermore, the results of micro-CT analysis revealed that the HFD+S group exhibited higher BMD, BV/TV, and Tb.N values but a lower Tb.Sp value than that of the HFD group. Serum glucose, leptin, and IL-1β concentrations were significantly correlated with the OARSI score. Histomorphological analysis revealed that OA was significantly exacerbated by the HFD-induced obesity and markedly alleviated by the simvastatin intervention. In details, simvastatin ameliorated the abnormal metabolic status and cartilage lesions, significantly increased aggrecan and collagen-II expression and decreased the expression of MMP-13 and leptin in cartilage. Furthermore, the results of micro-CT analysis revealed that the HFD+S group exhibited higher BMD, BV/TV, and Tb.N values but a lower Tb.Sp value than that of the HFD group. Serum glucose, leptin, and IL-1β concentrations were significantly correlated with the OARSI score. The HFD-induced obesity aggravates articular degeneration and deterioration in subchondral bone, which could be improved by the intervention of simvastatin, suggesting that simvastatin may be a potential candidate for amelioration of the progression of obesity induced-OA.

Keywords

• Osteoarthritis
• obesity
• cartilage
• subchondral bone
• simvastatin