The percentage of TUNEL positive chondrocytes following intraarticular fracture is much higher than that reported for chronic degenerative conditions such as osteoarthritis and rheumatoid arthritis. These data provide strong evidence that chondrocyte apoptosis is a consequence of intraarticular fracture and suggest that chondrocyte apoptosis may play a particularly significant role in the subsequent development of post-traumatic arthritis.

For the minority of people with lateral epicondylitis who do not respond to nonoperative treatment, surgical intervention is an option, but confusion exists because of the plethora of options. The surgical techniques for treating lateral epicondylitis can be grouped into three main categories: open, percutaneous, and arthroscopic. Our primary question was whether there was clear evidence suggesting one of these three approaches was superior in relieving pain, restoring strength, or reducing time to return to work. A 2002 Cochrane Collaboration Database review found no conclusions could be drawn regarding the efficacy of operative treatment given the lack of controlled trials. Although there is not enough literature to conduct a meta-analysis, we systematically reviewed the available literature to address our questions. Although there are advantages and disadvantages to each procedure, no technique appears superior by any measure. Therefore, until more randomized, controlled trials are done, it is reasonable to defer to individual surgeons regarding experience and ease of procedure.

The main objective of this study was to test the effectiveness of candidate apoptosis inhibitors in limiting chondrocyte apoptosis induced by collagen degradation. Primary human chondrocytes were isolated from normal articular cartilage and grown in monolayer culture. Collagenase was added to the cells in the presence and absence of caspase inhibitors and insulin like growth factor (1GF)-I . The amount of chondrocyte apoptosis was measured using an enzyme linked immunosorbent assay for nucleosomes, a specific and quantitative measure of apoptosis. Chondrocyte apoptosis was induced by collagenase treatment in both a time and dose dependent manner. The non-selective caspase inhibitor Z-VAD, the caspase-3 selective inhibitor Z-DEVD, and the growth factor insulin like growth factor (1GF)-I inhibited chondrocyte apoptosis induced by collagenase treatment. The caspase-l selective inhibitor Z-YVAD also blocked chondrocyte apoptosis under these conditions, in contrast to previous studies where caspase-1 inhibition failed to block apoptosis induced by agents such as the topoisomerase inhibitor camptothecin. These data demonstrate that the response of chondrocytes to caspase inhibition may be dependent upon the specific stimulus that initiates apoptosis. Furthermore, these findings suggest that multiple pathways involving both the initiation and execution of programmed cell death are potential targets for chondrocyte apoptosis inhibition therapy.

The primary objective of this study was to test the hypothesis that inhibition of mitochondrial permeability transition andlor inhibition of caspase family enzymes can block chondrocyte apoptosis induced by H202. Primary human chondrocytes were isolated from normal cartilage by enzymatic digestion. Apoptosis was induced by exposure to H202. Chondrocyte apoptosis was quantified using an ELISA for nucleosome formation. Independent confirmation of apoptosis was obtained by TUNEL analysis. H202 induced apoptosis in primary human chondrocytes in a time and dose dependent manner. The effects of candidate apoptosis inhibitors were then tested. Chondrocytes were pretreated with inhibitors of mitochondrial permeability transition, or one of three different caspase inhibitors, and then incubated with H202. Apoptosis was then measured after 16 h of exposure to H202. Pretreatment with inhibitors of mitochondrial permeability transition did not block apoptosis induced by H202. A non-selective caspase inhibitor, a caspase 3-selective inhibitor, and a caspase 1-selective inhibitor, all blocked chondrocyte apoptosis induced by H202. These results show that H 2 0 2 triggers chondrocyte apoptosis through caspase activation, independent of mitochondrial membrane permeability transition.

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