OBJECTIVE: Previous findings suggest that silent information regulator 2 ortholog 1 (SIRT1) plays essential roles in chondrocytes and prevents osteoarthritis (OA) development. The purpose of this study was to investigate the effects of intraperitoneal (i.p.) and intra-articular (i.a.) administration of the SIRT1 activator SRT2104, which has been approved for use in humans. DESIGN: OA was induced by destabilizing the medial meniscus in the knee joint of 12-week-old CL57BL/6J mice. The mice were divided into 3 groups, that is, the control group, SRT2104 i.p.-injection group, and SRT2104 i.a.-injection group. Tissues were harvested at 4, 8, 12, and 16 weeks postsurgery. OA progression was evaluated using the Osteoarthritis Research Society International (OARSI) score. The production of OA-related proteins in cartilage and synovium was examined by immunohistochemistry. RESULTS: OARSI scores in the control group were significantly higher at 8 and 12 weeks compared with other 2 groups. Immunohistochemical analysis showed that Sirt1 and type-2 collagen significantly increased, whereas MMP-13, ADAMTS-5, IL-1β, IL-6, cleaved caspase 3, PARP p85, acetylated NF-κB p65, and iNOS decreased significantly in cartilage tissues from the i.p. and i.a, SRT2104 groups. In the synovium, more iNOS-positive M1-like macrophages were observed in the control group than in the i.p. and i.a, SRT2104 groups, whereas more CD206-positive M2-like macrophages were detected in the i.p. and i.a. SRT2104 groups. CONCLUSIONS: Both i.p. and i.a. SRT2104 injection reduced OA progression in the mouse OA model, suggesting that SRT2104 can serve as a new treatment for OA.
OBJECTIVE: Previous findings suggest that silent information regulator 2 ortholog 1 (SIRT1) plays essential roles in chondrocytes and prevents osteoarthritis (OA) development. The purpose of this study was to investigate the effects of intraperitoneal (i.p.) and intra-articular (i.a.) administration of the SIRT1 activator SRT2104, which has been approved for use in humans. DESIGN: OA was induced by destabilizing the medial meniscus in the knee joint of 12-week-old CL57BL/6J mice. The mice were divided into 3 groups, that is, the control group, SRT2104 i.p.-injection group, and SRT2104 i.a.-injection group. Tissues were harvested at 4, 8, 12, and 16 weeks postsurgery. OA progression was evaluated using the Osteoarthritis Research Society International (OARSI) score. The production of OA-related proteins in cartilage and synovium was examined by immunohistochemistry. RESULTS: OARSI scores in the control group were significantly higher at 8 and 12 weeks compared with other 2 groups. Immunohistochemical analysis showed that Sirt1 and type-2 collagen significantly increased, whereas MMP-13, ADAMTS-5, IL-1β, IL-6, cleaved caspase 3, PARP p85, acetylated NF-κB p65, and iNOS decreased significantly in cartilage tissues from the i.p. and i.a, SRT2104 groups. In the synovium, more iNOS-positive M1-like macrophages were observed in the control group than in the i.p. and i.a, SRT2104 groups, whereas more CD206-positive M2-like macrophages were detected in the i.p. and i.a. SRT2104 groups. CONCLUSIONS: Both i.p. and i.a. SRT2104 injection reduced OA progression in the mouse OA model, suggesting that SRT2104 can serve as a new treatment for OA.
Authors: L Utomo; G J V M van Osch; Y Bayon; J A N Verhaar; Y M Bastiaansen-Jenniskens Journal: Osteoarthritis Cartilage Date: 2016-04-14 Impact factor: 6.576
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Authors: Xiaobo Zhu; Chien-Wei Lee; Hongtao Xu; Yu-Fan Wang; Patrick S H Yung; Yangzi Jiang; Oscar K Lee Journal: Arthritis Res Ther Date: 2021-04-10 Impact factor: 5.156