[en] OBJECTIVE: We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to determine if SIRT-1 enzymatic activity plays a protective role in cartilage homeostasis in vivo, by investigating mice with SIRT-1 mutations to characterize their cartilage. METHODS: Articular cartilage was harvested from the paws and knees of 5- and 6-month-old wild-type (WT) mice and mice homozygous for SIRT-1(tm2.1Mcby) (SIRT-1(y/y) ), an allele carrying a point mutation that encodes a SIRT-1 protein with no enzymatic activity (y/y mice). Mice ages 2 days old and 6-7 days old were also examined. Mouse joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. RESULTS: We found that articular cartilage tissue sections from y/y mice of up to 6 months of age contained reduced levels of type II collagen, aggrecan, and glycosaminoglycan compared to sections from WT mice. In contrast, protein levels of matrix metalloproteinase 8 (MMP-8), MMP-9, and MMP-13 were elevated in the cartilage of y/y mice. In addition, chondrocyte apoptosis was elevated in SIRT-1 mutant mice as compared to their WT littermates. Consistent with these observations, protein tyrosine phosphatase 1b was elevated in the y/y mice. CONCLUSION: Our in vivo findings in this animal model demonstrate that mice with defective SIRT-1 also have defective cartilage, with elevated rates of cartilage degradation with age. Hence, normal cartilage homeostasis requires enzymatically active SIRT-1 protein.
Disciplines :
Rheumatology
Author, co-author :
Gabay, Odile
Sanchez, Christelle ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Dvir-Ginzberg, Mona
Gagarina, Viktoria
Zaal, Kristien J.
Song, Yingjie
He, Xiao Hong
McBurney, Michael W.
Language :
English
Title :
Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model.
Publication date :
2013
Journal title :
Arthritis and Rheumatism
ISSN :
0004-3591
eISSN :
1529-0131
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Volume :
65
Issue :
1
Pages :
159-66
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2013 by the American College of Rheumatology.
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