INCREASED INSULIN-LIKE GROWTH-FACTOR-1 PRODUCTION BY HUMAN OSTEOARTHRITIC CHONDROCYTES IS NOT DEPENDENT ON GROWTH-HORMONE ACTION

Objective, To investigate insulin-like growth factor 1 (IGF-1) production in normal and osteoarthritis (OA) chondrocytes and to further examine the role of growth hormone (GH) in adult human cartilage and, in particular, in diseased tissue, Methods, IGF-1 production was measured with a radioimmunoassay, Binding assay, Northern blot, and reverse transcriptase polymerase chain reaction (RT-PCR) techniques were used for GH receptor (GHR) detection, The biological response to GH was estimated via IGF-1 production, Results, We observed that basal levels Of IGF-1 production were significantly higher in OA chondrocytes than in normal cells (P < 0.005). Adult human chondrocytes, however, were unresponsive to GH stimulation with regard to. IGF-1 production, as shown in dose-response (0-1,000 ng/ml) and time-course (days 1-8) studies, In addition, no specific I-125-GH binding was detected in either cell type, Northern blot analysis revealed a 5.5-kb GHR messenger RNA (mRNA) species, but semiquantitative RT-PCR revealed no difference in GHR mRNA expression by normal and OA chondrocytes, Conclusion. This study indicates that the elevated synthesis of IGF-1 by adult human OA chondrocytes occurs through a GH/GHR-independent mechanism, suggesting that other factors are capable of controlling local IGF-1 production in these cells.