INSULIN-LIKE GROWTH-FACTOR (IGF) RECEPTOR, IGF-I, INTERLEUKIN-1-BETA (IL-1-BETA), AND IL-6 MESSENGER-RNA EXPRESSION IN OSTEOARTHRITIC AND NORMAL HUMAN CARTILAGE

Insulin-like growth factor-I (IGF-I) stimulates the production of extr acellular matrix by cartilage cells and this action is mediated throug h the Type 1 IGF receptor. Expression of the genes for the IGF recepto r and for IGF-I was examined in normal and osteoarthritic (OA) human a rticular cartilage by in situ hybridization. RNA transcripts for Type 1 receptor were detected in all 73 tissue samples and in 80-100% of ch ondrocytes per section. Signal for the receptor was present in normal and OA cells, and the highest message levels were in the tissues exhib iting advanced pathology. Strong message signals in the cells of the m ore advanced lesions were also noted for IGF-I, whereas little or no I GF-I mRNA was detected in normal samples. Interleukin-1 beta (IL-1 bet a) induces degradation of extracellular matrix by cartilage cells, and expression of this gene was examined with digoxygenin-labeled oligonu cleotide probes. mRNA transcripts were detected in only one in five of the cartilage samples taken from OA joints. Unlike IGF-I, expression did not correlate with the degree of OA pathology and positive cells w ere demonstrated also in samples from young normal cartilage. IL-6 mRN A was present both in surface and deep cells of fibrillated OA cartila ge, but no signal was evident in histologically normal cartilage from OA tissue or in normal young joints.