Insulin-like growth factors maintain steady-state metabolism of proteoglycans in bovine articular cartilage explants

• Published in: Archives of biochemistry and biophysics Vol. 267; no. 2; p. 416
• Main Authors: Luyten, F P, Hascall, V C, Nissley, S P, Morales, T I, Reddi, A H
• Format: Journal Article
• Language: English
• Published: United States 01-12-1988
• Subjects: Animals; Cartilage, Articular - metabolism; Cattle; Cells, Cultured; DNA - metabolism; Dose-Response Relationship, Drug; Insulin-Like Growth Factor I - pharmacology; Insulin-Like Growth Factor II - pharmacology; Proteoglycans - biosynthesis; Proteoglycans - metabolism; Somatomedins - pharmacology
• ISSN: 0003-9861
• DOI: 10.1016/0003-9861(88)90047-1

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.