Sirt1-deficient mice exhibit an altered cartilage phenotype

Odile Gabay*, Kristien J. Zaal, Christelle Sanchez, Mona Dvir-Ginzberg, Viktoria Gagarina, Yingjie Song, Xiao Hong He, Michael W. McBurney

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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. Method: 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. Conclusion: 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.

Original languageAmerican English
Pages (from-to)613-620
Number of pages8
JournalJoint Bone Spine
Volume80
Issue number6
DOIs
StatePublished - Dec 2013
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by the Intramural Research Program of the National Institutes of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health .

Keywords

  • Animal models
  • Cartilage
  • Osteoarthritis
  • Sirtuin 1

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