Sah R L, Chen A C, Grodzinsky A J, Trippel S B
Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093.
Arch Biochem Biophys. 1994 Jan;308(1):137-47. doi: 10.1006/abbi.1994.1020.
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.
研究了碱性成纤维细胞生长因子（bFGF）和胰岛素样生长因子-I（IGF-I）对犊牛和成年牛软骨外植体中细胞和基质代谢的影响。在犊牛软骨中，bFGF对有丝分裂活性和合成代谢过程产生剂量依赖性的双向作用。添加3 ng/ml的bFGF可刺激细胞有丝分裂活性（总DNA）以及蛋白聚糖（[35S]硫酸盐掺入）、蛋白质（[3H]脯氨酸掺入）和胶原蛋白（[3H]羟脯氨酸形成）的合成，与基础培养基相比，蛋白聚糖沉积略有增加。然而，30 - 300 ng/ml的bFGF抑制有丝分裂活性和合成过程，与基础培养基相比加速了[35S]蛋白聚糖的释放，并导致培养期间蛋白聚糖沉积受到抑制。相比之下，用3 - 300 ng/ml的bFGF处理成年软骨不影响DNA含量，但以剂量依赖性方式刺激合成过程。碱性成纤维细胞生长因子对成年软骨中的基质分解代谢也有双向作用，3 ng/ml加速[35S]蛋白聚糖释放，但30 - 300 ng/ml的bFGF导致释放速率与基础培养基相当。尽管如此，即使在最大bFGF刺激下，成年牛软骨在培养期间蛋白聚糖仍出现净损失。向犊牛或成年牛软骨中添加3 - 300 ng/ml的IGF-I可刺激合成过程，并使代谢平衡向蛋白聚糖的净沉积转变。bFGF和IGF-I均未改变犊牛或成年牛软骨中[3H]羟脯氨酸的低基础释放率。因此，（i）bFGF和IGF-I对牛关节软骨的调节作用似乎具有年龄依赖性，并且（ii）bFGF能够促进合成代谢或分解代谢过程，因此可能在软骨代谢调节中发挥双重作用。
