Davidson J M, Klagsbrun M, Hill K E, Buckley A, Sullivan R, Brewer P S, Woodward S C
J Cell Biol. 1985 Apr;100(4):1219-27. doi: 10.1083/jcb.100.4.1219.
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.
软骨衍生生长因子（CDGF）是一种分子量约为18,000的阳离子多肽，由牛关节软骨制备而成；其他来源包括牛和人的肩胛软骨及肋软骨。先前的研究表明，CDGF可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。在本研究中，CDGF被证明可剂量依赖性地刺激大鼠胚胎成纤维细胞和来自肉芽组织的一群成纤维细胞中DNA和胶原蛋白的积累。CDGF还剂量依赖性地刺激培养的牛毛细血管内皮细胞的增殖。为了评估CDGF在体内的作用，我们将聚乙烯醇海绵皮下植入大鼠体内。植入后6天，向海绵中注射300微克部分纯化的CDGF，该剂量是考虑到与细胞培养相比海绵中的细胞数量而确定的。CDGF迅速从海绵中消失，在4小时时仅存在约10%的初始剂量。尽管其存在短暂，但CDGF在48小时时使海绵DNA含量相对增加2.6倍，在72小时时增加2.4倍。我们通过使用经肝素 - 琼脂糖色谱纯化至接近均一性的500纳克CDGF注射重复了海绵实验。纯化的CDGF在单次注射后48小时和72小时使海绵胶原蛋白、蛋白质和DNA含量显著增加。CDGF的作用被加热消除，且不受二硫键还原的影响。从形态学上看，CDGF未引发炎症反应，因此其对增殖的内皮细胞和成纤维细胞的作用可能是直接的。然而，海绵DNA含量的增加不能完全由DNA合成增加来解释，这表明募集可能是体内反应的一个重要组成部分。综上所述，CDGF对培养细胞和肉芽组织的作用表明，CDGF在体内的持续存在可能会大大增强其对伤口修复的作用。
