OSTEOGENIN AND RECOMBINANT BONE MORPHOGENETIC PROTEIN-2B ARE CHEMOTACTIC FOR HUMAN MONOCYTES AND STIMULATE TRANSFORMING GROWTH FACTOR-BETA-1 MESSENGER-RNA EXPRESSION
OSTEOGENIN AND RECOMBINANT BONE MORPHOGENETIC PROTEIN-2B ARE CHEMOTACTIC FOR HUMAN MONOCYTES AND STIMULATE TRANSFORMING GROWTH FACTOR-BETA-1 MESSENGER-RNA EXPRESSION
复制标题
DOI：
10.1073/pnas.89.24.11740
复制
发表时间：
1992-12-15
影响因子：
11.1
通讯作者：
REDDI, AH
中科院分区：
文献类型：
--
作者：
CUNNINGHAM, NS;PARALKAR, V;REDDI, AH
脱矿骨基质的皮下植入引发一系列发育事件，最终导致软骨内骨形成。在基质诱导植入物发育的早期阶段，观察到ED1、Ia阳性单核细胞-巨噬细胞，这表明在软骨内骨形成级联的初始阶段，骨诱导蛋白成骨素和相关骨形态发生蛋白（BMP）可能作为有效的化学引诱剂来招募循环单核细胞。在这项研究中，我们证明，在浓度为 10-100 fg/ml (0.3-3 fM) 时，天然牛成骨素和重组人 BMP-2B (rhBMP-2B) 可在体外诱导人血单核细胞的定向迁移。这种趋化反应与单核细胞上 BMP 结合位点（受体）的表达有关。每个细胞检测到约 750 个受体，表观解离常数为 200 pM。较高浓度 (0.1-30 ng/ml) 的成骨素和 rhBMP-2B 都会刺激人单核细胞中另一种调节分子、β1 型转化生长因子 (TGF-β1) 的 mRNA 表达。众所周知，TGF-β1 会引发一系列级联事件，从而导致基质生成。已知受 TGF-β 刺激的单核细胞会分泌多种趋化性和促有丝分裂细胞因子，这些细胞因子招募内皮细胞和间充质细胞并促进其合成胶原蛋白和相关基质成分。 TGF-β1 与这些其他细胞因子和基质成分协同调节趋化性、间充质增殖、分化、血管生成和细胞外基质的受控合成。我们的结果表明，成骨素和相关 BMP 通过对单核细胞募集和细胞因子合成产生深远影响，可能促进软骨内骨形成级联中的额外连续步骤。
Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type beta1 transforming growth factor (TGF-beta1) in human monocytes. TGF-beta1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-beta are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-beta1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.