Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor.

Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor.
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DOI:
10.1083/jcb.100.4.1219
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发表时间:
1985-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Woodward SC
Woodward SC
中科院分区:
其他
文献类型:
--
作者:
Davidson JM;Klagsbrun M;Hill KE;Buckley A;Sullivan R;Brewer PS;Woodward SC

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软骨衍生生长因子(CDGF)是一种约18,000 mol wt的阳离子多肽,由牛关节软骨制备;其他来源为牛和人肩胛骨和肋软骨。先前的研究表明,CDGF刺激培养的小鼠成纤维细胞以及来自各种来源的软骨细胞和内皮细胞的增殖。在这项研究中,CDGF被证明刺激剂量依赖性的DNA和胶原蛋白的大鼠胚胎成纤维细胞和肉芽组织来源的成纤维细胞的人口的积累。CDGF还刺激培养的牛毛细血管内皮细胞的增殖呈剂量依赖性。为了评价CDGF在体内的作用,我们将聚乙烯醇海绵植入大鼠皮下。植入后6天,海绵注射300微克部分纯化的CDGF,该剂量考虑了海绵中与细胞培养物相比的细胞数量。CDGF从海绵中迅速消失,在4小时时仅存在初始剂量的约10%。尽管其短暂存在,CDGF引起海绵DNA含量在48 h和72 h分别增加2.6倍和2.4倍。我们重复海绵实验,使用500 ng注射的CDGF纯化到接近同质的肝素-琼脂糖色谱。纯化的CDGF引起海绵胶原蛋白,蛋白质和DNA含量在48和72小时后,单次注射显着增加。CDGF的影响被废除的热量和不受二硫键的还原。形态学上,CDGF没有引起炎症反应,其对增殖的内皮细胞和成纤维细胞的影响,因此,可能是直接的。然而,海绵DNA含量的增加不能完全解释为DNA合成增加,这表明募集可能是体内反应的重要组成部分。总之,CDGF对培养细胞和肉芽组织的作用表明,体内持续存在的CDGF可大大增强其对伤口修复的作用。
Cartilage-derived growth factor (CDGF), a cationic polypeptide of approximately 18,000 mol wt, was prepared from bovine articular cartilage; other sources were bovine and human scapular and costal cartilage. Previous studies have shown that CDGF stimulates the proliferation of cultured mouse fibroblasts as well as chondrocytes and endothelial cells from various sources. In this study, CDGF was shown to stimulate dose-dependently the accumulation of DNA and collagen by rat embryo fibroblasts and a population of fibroblasts derived from granulation tissue. CDGF also stimulated the proliferation of cultured bovine capillary endothelial cells dose-dependently. To evaluate the effects of CDGF in vivo, we implanted polyvinyl alcohol sponges subcutaneously in rats. 6 d postimplantation, sponges were injected with 300 micrograms of partially purified CDGF, a dose which takes into account the cell numbers in the sponges as compared with cell cultures. CDGF rapidly disappeared from the sponges and only approximately 10% of the initial dose was present at 4 h. Despite its transient presence, CDGF caused a relative increase in sponge DNA content of 2.6-fold at 48 h and 2.4-fold at 72 h. We repeated the sponge experiment by using 500- ng injections of CDGF purified to near homogeneity by heparin-Sepharose chromatography. Purified CDGF caused significant increases in sponge collagen, protein, and DNA content at 48 and 72 h after a single injection. The effects of CDGF were abolished by heat and unaffected by reduction of disulfide linkages. Morphologically, CDGF did not evoke an inflammatory response, and its effect on proliferating endothelial cells and fibroblasts was, therefore, probably direct. However, increases in DNA content of sponges could not be fully accounted for by increased DNA synthesis, which suggests that recruitment may be an important component of the in vivo response. Taken together, the effects of CDGF on cultured cells and granulation tissue suggest that the sustained presence of CDGF in vivo may greatly enhance its effects upon wound repair.