Insulin-like growth factor (IGF) receptor, IGF-I, interleukin-1 beta (IL-1 beta), and IL-6 mRNA expression in osteoarthritic and normal human cartilage.

Abstract

Insulin-like growth factor-I (IGF-I) stimulates the production of extracellular matrix by cartilage cells and this action is mediated through the Type 1 IGF receptor. Expression of the genes for the IGF receptor and for IGF-I was examined in normal and osteoarthritic (OA) human articular cartilage by in situ hybridization. RNA transcripts for Type 1 receptor were detected in all 73 tissue samples and in 80-100% of chondrocytes per section. Signal for the receptor was present in normal and OA cells, and the highest message levels were in the tissues exhibiting advanced pathology. Strong message signals in the cells of the more advanced lesions were also noted for IGF-I, whereas little or no IGF-I mRNA was detected in normal samples. Interleukin-1 beta (IL-1 beta) induces degradation of extracellular matrix by cartilage cells, and expression of this gene was examined with digoxygenin-labeled oligonucleotide 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 were demonstrated also in samples from young normal cartilage. IL-6 mRNA was present both in surface and deep cells of fibrillated OA cartilage, but no signal was evident in histologically normal cartilage from OA tissue or in normal young joints.