Interleukin-1β induced premature senescence of articular chondrocytes
10.3760/cma.j.issn.1007-7480.2009.07.006
- VernacularTitle:白细胞介素-1β诱导关节软骨细胞发生过早衰老的机制
- Author:
Dongbao ZHAO
;
Zhengzheng SHAN
;
Shengming DAI
- Publication Type:Journal Article
- Keywords:
Osteoarthritis;
Chondrocytes;
Cell aging;
Interleukin-1
- From:
Chinese Journal of Rheumatology
2009;13(7):451-454,后插1
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study whether IL-1β, a catabolic factor of cartilage metabolism, induces premature senescence of articular chondrocytes, and whether caveolin-1 mediates IL-1β-induced cellular senescence. Methods Cultured human articular chondrocytes were stimulated with 10 ng/ml IL-1β. Cellular senescent phenotypes were analyzed by cellular morphology, cell growth arrest (flow cytometry), telomere erosion (Southern blotting), life span (population doublings), and specific senescence-associated β-galac-tosidase (SA-β-Gal) activity. Expression level of caveolin-1 was modulated by anti-sense oligunucleotide or transfection of caveolin-1 gene. Caveolin-1 protein was analyzed by Western blotting. Results Incubation of chondrocytes with IL-1β markedly increase the percentage of cells in G0/G1 phase and reduce the percentage in S phase. Single stimulation with IL-1β enables chondrocytes to become big and flat, and SA-β-Gal activity in chondrocytes is enhanced. Repeated stimulation with IL-Iβ resulted in accelerats erosion of mean telomere length, and shortens life span. Down-regulation of caveolin-1 with anti-sense oligonucleotide significantly inhibits the features of chondrocytes senescence induced by IL-1β. In contrast, caveolin-1 overexpreasion enhanced SA-β-Gal activity in the chondrocytes. Conclusion IL-1β induces features of stress-induced premature senescence and telemere-dependent replicative senescence of articular chondrocytes, which is mediated by caveolin-1. These data suggest that IL-1β induces premature senescence of articular chondro-cytes by upregulation of caveolin-1, which facilitates the development of osteoarthritis.
