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胰岛素样生长因子I和碱性成纤维细胞生长因子对生长板软骨细胞的调节

Regulation of growth-plate chondrocytes by insulin-like growth-factor I and basic fibroblast growth factor.

作者信息

Trippel S B, Wroblewski J, Makower A M, Whelan M C, Schoenfeld D, Doctrow S R

机构信息

Massachusetts General Hospital, Boston 02114.

出版信息

J Bone Joint Surg Am. 1993 Feb;75(2):177-89. doi: 10.2106/00004623-199302000-00004.

DOI:10.2106/00004623-199302000-00004
PMID:8423178
Abstract

A study was performed in order to investigate the possible functional roles of insulin-like growth-factor I (IGFI) and basic fibroblast growth factor (bFGF) in the regulation of mitotic and metabolic activity of growth-plate chondrocytes. Chondrocytes from the distal radial growth plates of calves and the costal physeal cartilage of rats were exposed to these factors, individually and in combination, in primary monolayer culture, to assess their effects. The data showed that bFGF had both a greater potency and a greater efficacy as a mitogen for bovine growth-plate chondrocytes than did IGF-I. The maximum incorporation of 3H-thymidine by bFGF was 8.3 times that in serum-free (control) cultures; the maximum stimulation of incorporation by IGF-I was 2.5 times that in the control medium. In contrast, IGF-I stimulated a maximum incorporation of 35S-sulfate into glycosaminoglycans that was 2.6 times that in the IGF-I serum-free control cultures, while bFGF had no effect or was mildly inhibitory. When used together, these two factors acted synergistically. Incorporation of 3H-thymidine was more than two times greater than the sum of the effects of the growth factors when used alone and 20.5 times greater than that of the growth factor-free control cultures. Physeal chondrocytes from six-day-old rats were mitotically more responsive to bFGF than to IGF-I, but they were more responsive to IGF-I when they had been derived from twenty-eight-day-old rats. Interaction between bFGF and factors in the serum enhanced the mitotic activity of the rat chondrocytes, but bFGF did not interact with IGF-I under the same experimental conditions. In the presence of bFGF, there was a reduction in the stimulation by IGF-I of incorporation of 35S-sulfate and a decrease in the percentage of chondrocytes containing alkaline phosphatase. These growth factors also influenced cellular morphology in culture. In the presence of IGF-I or serum, the rat chondrocytes manifested the polygonal morphology typical of chondrocytes in culture, while bFGF promoted a more elongated spindle shape. Removal of bFGF and replacement by IGF-I restored the polygonal morphology, indicating that this transition is reversible.

摘要

为了研究胰岛素样生长因子I(IGF-I)和碱性成纤维细胞生长因子(bFGF)在调节生长板软骨细胞有丝分裂和代谢活性中的可能功能作用,进行了一项研究。将来自小牛桡骨远端生长板的软骨细胞和大鼠肋骨骺软骨细胞在原代单层培养中单独或联合暴露于这些因子,以评估它们的作用。数据显示,作为牛生长板软骨细胞的促有丝分裂剂,bFGF比IGF-I具有更高的效力和更大的功效。bFGF使3H-胸腺嘧啶核苷的最大掺入量是无血清(对照)培养物中的8.3倍;IGF-I对掺入的最大刺激是对照培养基中的2.5倍。相反,IGF-I刺激35S-硫酸盐最大掺入糖胺聚糖的量是无IGF-I血清对照培养物中的2.6倍,而bFGF没有作用或有轻微抑制作用。当一起使用时,这两种因子起协同作用。3H-胸腺嘧啶核苷的掺入比单独使用生长因子时的作用总和大两倍多,比无生长因子对照培养物大20.5倍。来自6日龄大鼠的骨骺软骨细胞对bFGF的有丝分裂反应比对IGF-I更敏感,但当它们来自28日龄大鼠时,对IGF-I更敏感。bFGF与血清中的因子之间的相互作用增强了大鼠软骨细胞的有丝分裂活性,但在相同实验条件下,bFGF与IGF-I没有相互作用。在存在bFGF的情况下,IGF-I对35S-硫酸盐掺入的刺激减少,含碱性磷酸酶的软骨细胞百分比降低。这些生长因子也影响培养中的细胞形态。在存在IGF-I或血清的情况下,大鼠软骨细胞表现出培养中软骨细胞典型的多边形形态,而bFGF促进更细长的纺锤形。去除bFGF并用IGF-I替代可恢复多边形形态,表明这种转变是可逆的。

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