Sirtuin type 1 signaling pathway mediates the effect of diosgenin on chondrocyte metabolisms in osteoarthritis

Abstract

To observe the effect of sirtuin type 1 (SIRT1) signaling pathway on chondrocyte metabolism and mitochondrial oxidative stress, to explore roles of SIRT1 signaling pathway and diosgenin (Dgn) in pathogenesis of osteoarthritis (OA). Methods: To establish C57BL/6 mouse (13.5-18.0 g) model of OA. The chondrocytes were randomly assigned into 4 groups: an OA group, a Dgn+OA group, a Dgn+Sirtinol+OA group, and a Sirtinol+OA group. Expressions of SIRT1, acetylation-regulated transcription factor 1 (Ac-FOXO1), and Bax were detected in the 4 groups by Western blot. Changes in levels of succinate dehydrogenase, cytochrome C oxidase, and superoxide dismutase of mitochondrion in the 4 groups were observed. Results: Compared with the OA group, SIRT1 protein expression was increased in the OA+Dgn group (P<0.05), while the Ac-FOXO1 and Bax protein expressions were decreased (P<0.05), the SDH and COX expressions were decreased, and the SOD content was decreased (P<0.05). Compared with the OA+Dgn group, the SIRT1 expression in the OA+Dgn+Sirtinol group and the Sirtinol+OA group was increased (P<0.05), while the Ac-FOXO1 and Bax protein expressions were decreased (P<0.05). The SDH and COX expressions were decreased, the SOD content was decreased, the SDH and COX expressions were increased, and the SOD content was increased in the OA group (All P<0.05), while those indexes were reversed in the OA+Dgn+Sirtinol group and the Sirtinol+OA group (All P<0.05). Conclusion: The SIRT1 signaling pathway and OA are closely related to changes in chondrocyte apoptosis, in which Dgn may play a protective role in anti-OA by activating SIRT1 signaling pathway to inhibit apoptosis of chondrocytes and to increase chondrocyte mitochondrial oxidative stress capacity.