Insulin-like growth factors maintain steady-state metabolism of proteoglycans in bovine articular cartilage explants.
The influences of insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) on biosynthesis and catabolism of proteoglycans (PG) in bovine articular cartilage explants were examined to define their potential use in a chemically defined medium. In both short- (10 days) and long-term (40 days) cultures, 10 to 20 ng/ml IGF-I maintained PG synthesis at the same or higher levels than in a medium containing 20% fetal calf serum (FCS). Catabolic rates were slower in IGF-I medium than in medium with only 0.1% albumin, but somewhat faster than for cultures in medium with 20% FCS. In long-term cultures 20 ng/ml IGF-I maintained a steady-state condition; the amounts of glycosaminoglycan and DNA per hydroxyproline content were constant throughout the culture period. The half-maximal dose response for IGF-I on PG synthesis (4.5 ng/ml) was distinctly different from that for the IGF-I effect on PG catabolism (1.5 ng/ml), indicating that these two components of PG metabolism can be experimentally uncoupled. IGF-II was less potent than IGF-I in the same batches of articular cartilage; 100 ng/ml IGF-II increased PG synthesis and decreased PG catabolism relative to 0.1% albumin alone, but the responses were only about 60% of those for 5 ng/ml IGF-I. These results suggest that the chondrocytes regulate PG synthesis primarily via the type I IGF receptor and that the IGF-II response is through the same receptor. Evidence is also provided indicating that the cartilage explants initially contain about 50 ng IGF-I per gram wet weight; this matrix-bound IGF-I diffuses into the medium during culture. The chondrocytes synthesize little or no IGF-I that is released into the medium under the culture conditions used.
Luyten
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FP
Bone Cell Biology Section, National Institute of Dental Research, Bethesda, Maryland 20892.
Hascall
V C
VC
Nissley
S P
SP
Morales
T I
TI
Reddi
A H
AH
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology*
D011509:Proteoglycans; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA