Differential effects of bFGF and IGF-I on matrix metabolism in calf and adult bovine cartilage explants.
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.
Sah
R L
RL
Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093.
Chen
A C
AC
Grodzinsky
A J
AJ
Trippel
S B
SB
D000375:Aging / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008938:Mitosis / Q000187:drug effects; D009924:Organ Culture Techniques; D011392:Proline / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014316:Tritium
D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline