S. Dore et al., INCREASED INSULIN-LIKE GROWTH-FACTOR-1 PRODUCTION BY HUMAN OSTEOARTHRITIC CHONDROCYTES IS NOT DEPENDENT ON GROWTH-HORMONE ACTION, Arthritis and rheumatism, 38(3), 1995, pp. 413-419
Objective, To investigate insulin-like growth factor 1 (IGF-1) product
ion in normal and osteoarthritis (OA) chondrocytes and to further exam
ine the role of growth hormone (GH) in adult human cartilage and, in p
articular, in diseased tissue, Methods, IGF-1 production was measured
with a radioimmunoassay, Binding assay, Northern blot, and reverse tra
nscriptase polymerase chain reaction (RT-PCR) techniques were used for
GH receptor (GHR) detection, The biological response to GH was estima
ted via IGF-1 production, Results, We observed that basal levels Of IG
F-1 production were significantly higher in OA chondrocytes than in no
rmal cells (P < 0.005). Adult human chondrocytes, however, were unresp
onsive 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 typ
e, Northern blot analysis revealed a 5.5-kb GHR messenger RNA (mRNA) s
pecies, but semiquantitative RT-PCR revealed no difference in GHR mRNA
expression by normal and OA chondrocytes, Conclusion. This study indi
cates that the elevated synthesis of IGF-1 by adult human OA chondrocy
tes occurs through a GH/GHR-independent mechanism, suggesting that oth
er factors are capable of controlling local IGF-1 production in these
cells.