期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 1-14出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep43245
关键词
-
资金
- National Natural Science Foundation of China [81420108021, 81472116]
Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPK alpha 1 conditional knockout (AMPK alpha 1 cKO), AMPK alpha 2 conditional knockout (AMPK alpha 2 cKO) and AMPK alpha 1 alpha 2 conditional double knockout (AMPK alpha cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPK alpha cDKO mice. Furthermore, male but not female AMPK alpha cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKa cDKO mice resulted in an enhanced interleukin-1 beta(IL-1 beta)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-kappa B (phospho-NF-kappa B) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKa cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development.
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