Hauschka P V, Chen T L, Mavrakos A E
Harvard School of Dental Medicine, Boston, Massachusetts.
Ciba Found Symp. 1988;136:207-25. doi: 10.1002/9780470513637.ch13.
The presence of many types of polypeptide growth factors in the mineralized extracellular matrix of bone is now well established. These factors are generally referred to as bone-derived growth factors (BDGFs), and are similar, or possibly identical, to the following species; platelet-derived growth factor (PDGF); acidic and basic forms of fibroblast growth factor (aFGF, bFGF); transforming growth factor beta (TGF-beta); and insulin-like growth factor 1 (IGF-1). Several osteoinductive factors, such as bone morphogenetic protein (BMP) and osteogenin, a skeletal growth factor (SGF), and osteoblast-derived BDGFs, have also been identified. Complete description of the biological functions of these BDGFs which are relevant to bone will ultimately require specific bioassays involving specific cell types in vitro, as well as in vivo animal implant models. Studies with primary rat osteoblast-like cells exposed either to mixed BDGFs, pure TGF-beta, or heparin-purified PDGF, aFGF, or bFGF from bovine bone have shown a general dose-dependent mitogenic effect. Phenotypic changes which accompany the BDGF-induced wave of proliferation include: decreased osteocalcin secretion and a reduction in 1,25-(OH)2 vitamin D3-stimulated osteocalcin synthesis; reduced alkaline phosphatase specific activity; decreased cyclic AMP responsiveness to parathyroid hormone (PTH); and increased collagen synthesis. Bone exhibits the most complex spectrum of growth factor activities of any tissue yet described. In bovine bone powder free of blood and cartilage contamination, the volume concentration of mitogens is up to 20 times greater than that in serum. Bone cells and other indigenous cell types must be considered as possible sources of the BDGFs, in addition to sequestration from blood. Mechanisms for the unmasking or release of BDGFs from the mineralized matrix that result in local action on osteoblasts, endothelial cells, and other target cells are undoubtedly important for the development and maintenance of bone tissue.
现在已经充分证实，在骨的矿化细胞外基质中存在多种类型的多肽生长因子。这些因子通常被称为骨源性生长因子（BDGFs），与以下几种物质相似或可能相同：血小板衍生生长因子（PDGF）；成纤维细胞生长因子的酸性和碱性形式（aFGF、bFGF）；转化生长因子β（TGF-β）；以及胰岛素样生长因子1（IGF-1）。还鉴定出了几种骨诱导因子，如骨形态发生蛋白（BMP）和成骨素、一种骨骼生长因子（SGF）以及成骨细胞衍生的BDGFs。要全面描述这些与骨相关的BDGFs的生物学功能，最终需要进行涉及体外特定细胞类型以及体内动物植入模型的特定生物测定。对原代大鼠成骨样细胞进行的研究表明，将其暴露于混合BDGFs、纯TGF-β或从牛骨中用肝素纯化的PDGF、aFGF或bFGF中时，会产生一般的剂量依赖性促有丝分裂作用。伴随BDGF诱导的增殖波出现的表型变化包括：骨钙素分泌减少以及1,25-(OH)2维生素D3刺激的骨钙素合成减少；碱性磷酸酶比活性降低；环磷酸腺苷对甲状旁腺激素（PTH）的反应性降低；以及胶原蛋白合成增加。在已描述的所有组织中，骨展现出最为复杂的生长因子活性谱。在无血液和软骨污染的牛骨粉中，有丝分裂原的体积浓度比血清中的高20倍。除了从血液中隔离外，骨细胞和其他固有细胞类型也必须被视为BDGFs的可能来源。导致BDGFs从矿化基质中暴露或释放从而对成骨细胞、内皮细胞和其他靶细胞产生局部作用的机制，无疑对骨组织的发育和维持至关重要。
