Increased insulin‐like growth factor 1 production by human osteoarthritic chondrocytes is not dependent on growth hormone action

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Abstract
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 125I‐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.

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