EFFECT OF LONG-TERM VOLUNTARY EXERCISE ON THE INDUCTION OF OSTEOARTHRITIS BY A VERY HIGH-FAT DIET IN AGED MICE

senescence. We have previously reported a significant reduction in the percentage of proliferating cells, but no significant change in the percentage of apoptosing cells, in tissue biopsies taken from tendinopathy patients seven weeks after local GC injection compared to in biopsies taken from the same patients immediately prior to injection. In the present study we found the percentage of p53-positive cells in tissue biopsies was significantly higher (p¼0.03) post-GC injection compared to pre-GC injection. The percentage of p21-positive cells also tended to be higher (p¼0.06) post-GC injection compared to preinjection. Conclusions: Results from this study demonstrate GCs activate the p53/ p21 senescence-inducing pathway in vitro and provide compelling evidence that this pathway is also activated following local GC injection in vivo. The loss of normal cell functionality associated with senescence has been linked with disease and degeneration in a number of different tissues. Given the apparent irreversible nature of the senescent phenotype, GC-induced senescence is likely to have long-term detrimental consequences on tissue. The fact that we observed a marked increase in p53 expression sevenweeks following GC injection supports the notion that the effects of local GC injection on tendon tissue are not transient. Senescence induction by GCs may exacerbate the underlying tissue pathology responsible for the pain for which the GCs were prescribed to treat.