Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice

Objective: A growing body of evidence indicates that the protein deacetylase, SirT1, affects chondrocyte biology and survival. This report aims to evaluate in vivo attributes of SirT1 in cartilage biology of 129/J murine strains. Methods: Heterozygous haploinsufficient (SirT1^+/-) and wild-type (WT; SirT1^+/+) 129/J mice aged 1 or 9 months were systematically compared for musculoskeletal features, scored for osteoarthritis (OA) severity, and monitored for chondrocyte apoptosis in articular cartilage. Sections of femorotibial joints were stained for type II collagen and aggrecan. Protein extracts from articular chondrocytes were isolated and immunoblotted for SirT1 and active caspase 3. Results: Phenotypic observations show that, at 1 month of age, SirT1^+/- mice were smaller than WT and showed a significant decrease in full-length SirT1 (FLSirT1; 110 kDa) protein levels. Levels of FLSirT1 were further decreased in both strains at 9 months. Immunoblot assays for 9-month-old strains revealed the presence of the inactive cleaved SirT1 variant (75 SirT1; 75 kDa) in WT mice, which was undetected in age-matched SirT1^+/- mice. Nine-month-old SirT1^+/- mice also showed increased OA and increased levels of apoptosis compared with age-matched WT mice. Conclusion: The data suggest that the presence of 75 SirT1 may prolong viability of articular chondrocytes in adult (9-month-old) mice.