Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells
Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells
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DOI：
10.1006/excr.1996.0005
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发表时间：
1996-01-10
影响因子：
3.7
通讯作者：
Hauschka, PV
中科院分区：
文献类型：
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作者：
Asahina, I;Sampath, TK;Hauschka, PV
成骨蛋白-1（OP-1，BMP-7），转化生长因子-β超家族中的骨形态发生蛋白，在体内诱导软骨内骨形成，但OP-1在骨生成中的作用机制尚未建立。三种不同分化阶段的小鼠克隆细胞系对重组人OP-1表现出分级反应：小鼠胚胎癌ATDC 5细胞，具有成软骨细胞分化的潜力;成骨样MC 3 T3-E1细胞来源于小鼠颅骨;多能成纤维细胞C3 H10 T1/2细胞来源于小鼠胚胎结缔组织。我们发现OP-1作用于早期间充质祖细胞（ATDC 5，C3 H10 T1/2）以诱导成软骨细胞分化，而OP-1强烈增强定向成骨细胞（MC 3 T3-E1）的成骨表型，这可能解释了其在体内诱导软骨内骨化级联反应。比较成骨细胞、成软骨细胞和脂肪细胞分化的标志物。OP-1对ATDC 5具有强烈的促有丝分裂作用，显示剂量依赖性（2.5-80 ng/ml）诱导阿尔新蓝染色、碱性磷酸酶活性和胶原蛋白If和IX型以及基质Gla蛋白的mRNA表达。MC 3 T3-E1细胞对OP-1不增殖或用阿尔新蓝染色，但表达升高水平的碱性磷酸酶和骨钙素。虽然C3 H10 T1/2的低剂量OP-1处理仅诱导充满脂滴的脂肪细胞样细胞，但高剂量（500 ng/ml）导致相同的细胞也表现出软骨细胞性质。因此，OP-1可以根据靶细胞的阶段和潜能，沿着软骨内骨化途径的要素沿着诱导分化。(C)出版社：Academic Press，Inc.
Osteogenic protein-1 (OP-1, BMP-7), a bone morphogenetic protein in the transforming growth factor-beta superfamily, induces endochondral bone formation in vivo but the mechanism of action of OP-l in osteogenesis is not yet established. Three murine clonal cell lines in different stages of differentiation exhibit graded responses to recombinant human OP-1: the mouse embryonal carcinoma ATDC5 cell, with potential for chondroblastic differentiation; the osteoblastlike MC3T3-E1 cell derived from mouse calvaria; and the multipotent fibroblastic C3H10T1/2 cell derived from mouse embryo connective tissue. We show that OP-l acts on early stage mesenchymal progenitor cells (ATDC5, C3H10T1/2) to induce chondroblastic differentiation, while OP-l strongly enhances the osteoblastic phenotype of committed osteoblasts (MC3T3-E1), possibly explaining its induction of the endochondral ossification cascade in vivo. Markers of osteoblastic, chondroblastic, and adipocytic differentiation are compared. OP-l is strongly mitogenic for ATDC5, showing dose-dependent (2.5-80 ng/ml) induction of Alcian blue staining, alkaline phosphatase activity, and mRNA expression for collagen types If and IX, and matrix Gla protein. MC3T3-E1 cells do not proliferate or stain with Alcian blue in response to OP-1, but express elevated levels of alkaline phosphatase and osteocalcin. While low-dose OP-l treatment of C3H10T1/2 induces only adipocyte-like cells filled with lipid droplets, a high dose (500 ng/ml) causes the same cells to also exhibit chondrocytic properties. Thus, OP-l can induce differentiation along elements of the endochondral ossification pathway according to the stage and potential of the target cell. (C) 1996 Academic Press, Inc.