CHONDROCYTE CYTOKINE AND GROWTH-FACTOR EXPRESSION IN MURINE OSTEOARTHRITIS

Eighty-five percent of male STR/ort mice develop osteoarthritic lesion s of the knee joint by 35 weeks of age. We have developed a non-radioa ctive in-situ hybridization method using digoxigenin-labeled oligonucl eotide probes to study the expression of the cytokines interleukin (IL ) 1 alpha, II-1 beta and IL-6 and the growth factors insulin-like grow th factor-1 (IGF-1) and transforming growth factor beta (TCF beta 1) d uring the development of osteoarthritis (OA) in this model. Age-and se x-matched CBA mice, which do not develop OA, showed no detectable expr ession of any of the cytokines or growth factors studied. In contrast, 20-week-old STR/ort mice with no OA lesions showed positive expressio n [positive: (+)] for all the cytokines and growth factors studied. At 35 weeks of age, STR/ort mice with varying grades of OA showed positi ve (+) or strong (++) signals for both cytokines and growth factors th roughout the tibial articular cartilage. The strongest signal was seen in areas where OA lesions were present. In areas of histologically-no rmal cartilage adjacent to the lesions, the signals were still positiv e but weaker. Fifty-week-old STR/ort mice with OA lesions showed a sim ilar 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 compa red with those with OA lesions. These mice may be indicative of those STR/ort mice which do not develop Oh. 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 p relesional stages of OA with anabolic effects predominating. At later stages of OA, the effects of catabolic factors appear to predominate a nd osteoarthritic lesions become evident.