AMPK deficiency in chondrocytes accelerated the progression of instability induced and ageing associated osteoarthritis in adult mice
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 AMPKa1 conditional knockout (AMPKa1 cKO) AMPKa2 conditional knockout (AMPKa2 cKO) and AMPKa1a2 conditional double knockout (AMPKa cDKO) mice, we found that compared with wild type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKa cDKO mice. Furthermore, male but not female AMPKa 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 1b (IL 1b) stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase 3 (MMP 3) MMP 13 and phospho nuclear factor kB (phospho NF kB) 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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