INSULIN-LIKE GROWTH-FACTORS MAINTAIN STEADY-STATE METABOLISM OF PROTEOGLYCANS IN BOVINE ARTICULAR-CARTILAGE EXPLANTS

INSULIN-LIKE GROWTH-FACTORS MAINTAIN STEADY-STATE METABOLISM OF PROTEOGLYCANS IN BOVINE ARTICULAR-CARTILAGE EXPLANTS
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DOI:
10.1016/0003-9861(88)90047-1
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发表时间:
1988-12-01
影响因子:
3.9
通讯作者:
REDDI, AH
REDDI, AH
中科院分区:
生物学3区
文献类型:
--
作者:
LUYTEN, FP;HASCALL, VC;REDDI, AH

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研究了胰岛素样生长因子I(IGF-I)和胰岛素样生长因子II(IGF-II)对牛关节软骨外植体中蛋白聚糖(PG)生物合成和催化的影响,以确定其在化学成分确定的培养基中的潜在用途。在短期(10天)和长期(40天)的文化,10至20 ng/ml的IGF-I保持PG合成在相同或更高的水平比在培养基中含有20%胎牛血清(FCS)。IGF-I培养基中的分解代谢速率比仅含0.1%白蛋白的培养基中慢,但比含20%FCS的培养基中的培养物稍快。在长期培养中,20 ng/ml IGF-I维持稳态条件;在整个培养期间,每羟脯氨酸含量的糖胺聚糖和DNA的量是恒定的。IGF-I对PG合成的半数最大剂量反应(4.5 ng/ml)与IGF-I对PG催化剂的作用(1.5 ng/ml)明显不同,表明PG代谢的这两种组分可以在实验上解耦。在相同批次的关节软骨中,IGF-II的效力低于IGF-I;相对于单独的0.1%白蛋白,100 ng/ml IGF-II增加了PG合成并降低了PG催化剂,但反应仅为5 ng/ml IGF-I的约60%。这些结果表明,软骨细胞调节PG合成主要通过I型IGF受体和IGF-II的反应是通过相同的受体。还提供了证据表明,软骨外植体最初含有约50 ng IGF-I/克湿重,这种基质结合的IGF-I扩散到培养基中培养期间。软骨细胞合成很少或不合成IGF-I,IGF-I在所使用的培养条件下释放到培养基中。
The influence 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 glycosaminoglycans 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 release into the medium under the culture conditions used.