U.S. Department of Defense


Date of this Version



Joint Bone Spine 80 (2013) 613–620


This article is a U.S. government work, and is not subject to copyright in the United States.


tObjective: We previously demonstrated that Sirt1 regulates apoptosis in cartilage in vitro. Here weattempt to examine in vivo cartilage homeostasis, using Sirt1 total body knockout (KO) mice.Method: Articular cartilage was harvested from hind paws of 1-week and 3-week-old mice carrying wildtype (WT) or null Sirt1 gene. Knees of Sirt1 haploinsufficient mice also were examined, at 6 months. Jointcartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures.Results: We found that articular cartilage tissue sections from Sirt1 KO mice up to 3 weeks of age exhibitedlow levels of type 2 collagen, aggrecan, and glycosaminoglycan content. In contrast, protein levels of MMP-13 were elevated in the Sirt1 KO mice, leading to a potential increase of cartilage breakdown, alreadyshown in the heterozygous mice. Additional results showed elevated chondrocyte apoptosis in Sirt1 KOmice, as compared to WT controls. In addition to these observations, PTP1b (protein tyrosine phosphataseb) was elevated in the Sirt1 KO mice, in line with previous reports.Conclusion: The findings from this animal model demonstrated that Sirt1 KO mice presented an alteredcartilage phenotype, with an elevated apoptotic process and a potential degradative cartilage process.