Delayed Progression of Meniscal Degeneration in Silent Information Regulator 2 Ortholog 1 Knock-In Mouse.

Abstract

This study aimed to examine the inhibitory effects of silent information regulator 2 ortholog 1 (SIRT1) on meniscal degeneration. First, SIRT1 expression in human and mouse menisci was examined using reverse transcription polymerase chain reaction (PCR) and immunostaining, which confirmed its presence. Meniscus degeneration in wild-type (WT) and SIRT1-knock-in (KI) mice was evaluated at 1, 3, 6, 9, and 12 months of age using the Kwok scoring system. The meniscus degeneration score for the anterior segment was significantly lower in KI mice than in WT mice at 9 and 12 months of age (p&#x2009;<&#x2009;0.01). Furthermore, osteoarthritis (OA) was induced in 3-month-old mice via medial meniscus destabilization to evaluate meniscal degeneration during OA progression. In the OA model, the meniscus degeneration score for anterior segment in KI mice was significantly lower than those in WT mice at 8, 12, and 16 weeks post-surgery (p&#x2009;<&#x2009;0.01). Additionally, RNA was extracted from the menisci of 1- and 3-month-old KI and WT mice, and gene expression was analyzed using real-time PCR. Gene expression analysis showed significantly higher levels of Sirt1, Col1a1, Col2a1, and aggrecan, and lower levels of Mmp-3, Mmp-13, and Adamts-5 in KI mice at 3 months compared with WT mice. These findings suggest that SIRT1 may delay meniscal degeneration by modulating the expression of cartilage matrix genes and matrix-degrading enzymes.