Chondrocyte cytokine and growth factor expression in murine osteoarthritis.

Eighty-five percent of male STR/ort mice develop osteoarthritic lesions of the knee joint by 35 weeks of age. We have developed a non-radioactive in-situ hybridization method using digoxigenin-labeled oligonucleotide probes to study the expression of the cytokines interleukin (IL) 1 alpha, Il-1 beta and IL-6 and the growth factors insulin-like growth factor-1 (IGF-1) and transforming growth factor beta (TGF beta 1) during the development of osteoarthritis (OA) in this model. Age- and sex-matched CBA mice, which do not develop OA, showed no detectable expression of any of the cytokines or growth factors studied. In contrast, 20-week-old STR/ort mice with no OA lesions showed positive expression [positive: (+)] for all the cytokines and growth factors studied. At 35 weeks of age, STR/ort mice with varying grades of OA showed positive (+) or strong (++) signals for both cytokines and growth factors throughout the tibial articular cartilage. The strongest signal was seen in areas where OA lesions were present. In areas of histologically-normal cartilage adjacent to the lesions, the signals were still positive but weaker. Fifty-week-old STR/ort mice with OA lesions showed a similar pattern of expression to 35-week-old mice. Thirty-five or 50-week-old STR/ort mice with no OA lesions had much reduced expression compared with those with OA lesions. These mice may be indicative of those STR/ort mice which do not develop OA. The results seen in the STR/ort together with previous biochemical analyses are consistent with an up-regulation of anabolic growth factors and catabolic cytokines in the prelesional stages of OA with anabolic effects predominating. At later stages of OA, the effects of catabolic factors appear to predominate and osteoarthritic lesions become evident.