Stimulation of proteoglycan synthesis by triamcinolone acetonide and insulin-like growth factor 1 in normal and arthritic murine articular cartilage.
OBJECTIVE
During experimentally induced arthritis, inhibition of proteoglycan synthesis is one of the mechanisms leading to cartilage destruction. Disturbed anabolic signalling might contribute to this impaired chondrocyte proteoglycan synthesis. We investigated the effects of insulin-like growth factor 1 (IGF-1) and the glucocorticoid, triamcinolone acetonide, on in vitro chondrocyte proteoglycan synthesis of articular cartilage obtained from normal and arthritic mouse knee joints.


METHODS
Proteoglycan synthesis was measured by 35S sulfate incorporation and the hydrodynamic volume of newly synthesized proteoglycans was analyzed with gel chromatography.


RESULTS
Culturing normal cartilage with IGF-1 resulted in significant enhancement of chondrocyte proteoglycan synthesis. Concerning the hydrodynamic volume of newly synthesized proteoglycans after culture with IGF-1, proteoglycan monomers with large hydrodynamic size, similar to those synthesized immediately after dissection were observed. In arthritic cartilage, IGF-1 failed to stimulate proteoglycan synthesis and only proteoglycans with relatively small dimensions were produced. However, in the presence of the steroid triamcinolone acetonide, synthesis of hydrodynamically large proteoglycans were found in arthritic as well as normal cartilage.


CONCLUSIONS
Our observations indicate that steroids may play a critical role in maintaining cartilage integrity in both normal and arthritic cartilage.
Verschure
P J
PJ
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
van der Kraan
P M
PM
Vitters
E L
EL
van den Berg
W B
WB
D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011509:Proteoglycans / Q000096:biosynthesis* / Q000737:chemistry / Q000187:drug effects; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I; D014222:Triamcinolone Acetonide