Chondrocyte nonresponsiveness to insulin-like growth factor 1 in experimental arthritis.
Inhibition of chondrocyte proteoglycan (PG) synthesis is one of the mechanisms leading to cartilage destruction in joint inflammation. Using murine cartilage from normal and arthritic knee joints, we examined this process. We found that for normal, anatomically intact murine articular cartilage, insulin-like growth factor 1 (IGF-1) is a potent anabolic factor. Recombinant IGF-1 at physiologic concentrations in a completely synthetic medium sustained PG synthesis, at the in vivo rate, of patellar cartilage in organ culture. Using an experimental arthritis model, we found that cartilage from an arthritic joint could not be stimulated in vitro with IGF-1. This nonresponsiveness was not caused by a generalized metabolic inhibition of the chondrocytes, because PG synthesis in arthritic cartilage could still be stimulated by forskolin, an activator of adenylate cyclase. Our data suggest that during joint inflammation, inhibition of chondrocyte PG synthesis is, at least partially, caused by a defect in the IGF-1 responsiveness of the chondrocyte. We propose this finding as a possible pathogenetic mechanism for cartilage destruction in joint diseases.
Schalkwijk
J
J
Department of Rheumatology, University Hospital St. Radboud, Nijmegen, The Netherlands.
Joosten
L A
LA
van den Berg
W B
WB
van de Putte
L B
LB
D000818:Animals; D001168:Arthritis / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007719:Knee Joint; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000096:biosynthesis*; D015290:Second Messenger Systems; D013002:Somatomedins / Q000494:pharmacology*; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes
D011509:Proteoglycans; D013002:Somatomedins; D013431:Sulfates; D013462:Sulfur Radioisotopes; D005576:Colforsin; D007334:Insulin-Like Growth Factor I