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  • Title: Differential effects of bFGF and IGF-I on matrix metabolism in calf and adult bovine cartilage explants.
    Author: Sah RL, Chen AC, Grodzinsky AJ, Trippel SB.
    Journal: Arch Biochem Biophys; 1994 Jan; 308(1):137-47. PubMed ID: 8311446.
    Abstract:
    The effects of basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I) on cell and matrix metabolism in calf and adult bovine cartilage explants were examined. In calf cartilage, bFGF elicited dose-dependent and bi-directional effects on mitotic activity and anabolic processes. Addition of bFGF at 3 ng/ml stimulated cell mitotic activity (total DNA) and synthesis of proteoglycan ([35S]sulfate incorporation), protein ([3H]proline incorporation), and collagen (formation of [3H]hydroxyproline), and resulted in a slight increase in proteoglycan deposition compared to basal medium. However, 30-300 ng/ml of bFGF inhibited mitotic activity and synthetic processes, accelerated [35S]proteoglycan release compared to basal medium, and resulted in an inhibition of proteoglycan deposition during the culture period. In contrast, treatment of adult cartilage with 3-300 ng/ml of bFGF did not affect the DNA content but did stimulate synthetic processes in a dose-dependent manner. Basic FGF also had bidirectional effects on matrix catabolism in adult cartilage, with 3 ng/ml accelerating [35S]proteoglycan release, but 30-300 ng/ml of bFGF resulting in release rates comparable to that in basal medium. Nonetheless, even with maximal bFGF stimulation, adult bovine cartilage suffered a net loss of proteoglycan during culture. Addition of 3-300 ng/ml of IGF-I to either calf or adult bovine cartilage stimulated synthetic processes and shifted the metabolic balance toward a net deposition of proteoglycan. Neither bFGF nor IGF-I altered the low basal rate of [3H]hydroxyproline release from either calf or adult bovine cartilage. Thus, (i) the regulatory effects of bFGF and IGF-I on bovine articular cartilage appear age-dependent, and (ii) bFGF is capable of promoting either anabolic or catabolic processes, and may therefore serve a dual role in the regulation of cartilage metabolism.
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