Insulin-like growth factor-1 suppresses pyrophosphate elaboration by transforming growth factor beta1-stimulated chondrocytes and cartilage.
Our objective was to examine the effect of insulin-like growth factor-1 (IGF-1) on extracellular pyrophosphate (ePPi) elaboration by porcine cartilage. These studies further define the factors influencing ePPi accrual, a key step in calcium pyrophosphate dihydrate (CPPD) crystal formation. ePPi was measured in adult porcine organ and monolayer culture media in the presence of IGF-1, transforming growth factor beta-1 (TGFbeta-1), IGF-1 antibody and synovial fluid (SF). As previously shown, TGFbeta-1 stimulated ePPi elaboration by cartilage and chondrocytes. IGF-1 significantly inhibited the stimulatory effect of TGFbeta-1 on ePPi elaboration by both cartilage explants and chondrocytes. Anti-IGF-1 antibody blocked this inhibition. Anti-IGF-1 antibody also decreased the inhibitory effect of SF on ePPi elaboration, suggesting the presence of active IGF-1. These results support an important regulatory role for IGF-1 in cartilage ePPi elaboration. IGF-1 inhibited the effects of the ePPi-stimulatory factor TGFbeta-1 and thus may protect normal joints from excess accumulation of ePPi and subsequent CPPD crystal formation.
Olmez
U
U
The Division of Rheumatology, Medical College of Wisconsin, Milwaukee, USA.
Ryan
L M
LM
Kurup
I V
IV
Rosenthal
A K
AK
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D011756:Diphosphates / Q000037:antagonists & inhibitors*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D013431:Sulfates / Q000378:metabolism; D013552:Swine; D013582:Synovial Fluid / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
D011756:Diphosphates; D013431:Sulfates; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I