title: Sirt1-deficient mice exhibit an altered cartilage phenotype.
abstract: OBJECTIVE
  We previously demonstrated that Sirt1 regulates apoptosis in cartilage in vitro. Here we attempt to examine in vivo cartilage homeostasis, using Sirt1 total body knockout (KO) mice.
  
  
  METHODS
  Articular cartilage was harvested from hind paws of 1-week and 3-week-old mice carrying wild type (WT) or null Sirt1 gene. Knees of Sirt1 haploinsufficient mice also were examined, at 6 months. Joint cartilage 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 exhibited low 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, already shown in the heterozygous mice. Additional results showed elevated chondrocyte apoptosis in Sirt1 KO mice, as compared to WT controls. In addition to these observations, PTP1b (protein tyrosine phosphatase b) was elevated in the Sirt1 KO mice, in line with previous reports.
  
  
  CONCLUSIONS
  The findings from this animal model demonstrated that Sirt1 KO mice presented an altered cartilage phenotype, with an elevated apoptotic process and a potential degradative cartilage process.
authors.affiliation: Cartilage Biology and Orthopedic Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD, USA. Electronic address: gabayo@mail.nih.gov.
authors.forename: Odile
authors.initials: O
authors.lastname: Gabay
authors.forename: Kristien J
authors.initials: KJ
authors.lastname: Zaal
authors.forename: Christelle
authors.initials: C
authors.lastname: Sanchez
authors.forename: Mona
authors.initials: M
authors.lastname: Dvir-Ginzberg
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gagarina
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Song
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: He
authors.forename: Michael W
authors.initials: MW
authors.lastname: McBurney
mesh_terms: D000818:Animals; D017209:Apoptosis; D002357:Cartilage Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000737:chemistry* / Q000473:pathology; D019902:Chondrocytes / Q000502:physiology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
keywords: Animal models; Cartilage; Osteoarthritis; Sirtuin 1