Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells
Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells
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DOI：
10.1006/cyto.2000.0760
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发表时间：
2000-11-01
期刊：
影响因子：
3.8
通讯作者：
Erlacher, L
中科院分区：
文献类型：
--
作者：
Gruber, R;Mayer, C;Erlacher, L
软骨衍生的形态发生蛋白1和2（CCR 1 -1和CCR 2 -2）是骨形态发生蛋白（BMP）家族的成员，在胚胎骨骼发育中起重要作用。在整个成年过程中，骨髓源性前体细胞保持其响应局部生长因子分化成骨细胞的能力。本研究检测了CMPs-1、CMPs-2、BMP-6和成骨蛋白1（OP-1）在骨髓基质细胞（BMSC）中的成骨潜能，并研究了CDMP/BMP及其各自的激活素受体样激酶（ALK）受体的内源性表达。和OP-1在无血清条件下以剂量依赖性方式刺激成骨谱系的进展，如通过碱性磷酸酶活性和骨钙素合成所评估的。与BMP相反，CCRs-1和尤其是CCRs-2显著较少成骨，通过北方印迹分析证实。此外，BMSC被证明内源性表达cAMP-2、BMP-2至-6和ALK-1、-2、-3、-5和-6。通过RT-PCR对BMSC的表型表征显示脂肪标记物adipsin和前软骨细胞标记物前胶原IIA型的转录物;然而，即使在生长因子处理后，我们也无法检测到成熟软骨标记物前胶原IIB型和聚集蛋白聚糖。我们的数据表明，CDMP-I、CDMP-2、BMP-6和OP-1增强BMSC中的成骨表型，其中CDMP的成骨性明显低于BMP。多种CDMP/BMP及其各自的ALK受体的内源性表达表明这些生长因子可能参与骨髓祖细胞的成骨分化，（C）2000 Academic Press。
Cartilage-derived morphogenetic proteins 1 and 2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family which play an important role in embryonic skeletal development. Throughout adult life, bone marrow-derived precursor cells maintain their ability to differentiate into osteoblasts in response to local growth factors. This study examines the osteogenic potential of CDMP-1, CDMP-2, BMP-6 and osteogenic protein 1 (OP-l) in bone marrow stromal cells (BMSC) and investigates the endogenous expression of CDMPs/BMPs and their respective activin receptor-like kinase (ALK) receptors, A 4-day exposure of BMSC to CDMP-1, CDMP-2, BMP-6, and OP-1 under serum-free conditions stimulated the progression of the osteogenic lineage in a dose-dependent manner as evaluated by alkaline phosphatase activity and osteocalcin synthesis, In contrast to the BMPs, CDMP-1 and especially CDMP-2 were significantly less osteogenic, as confirmed by Northern blot analysis. Moreover, BMSC were shown to express endogenously CDMP-2, BMP-2 to -6 and ALK-1, -2, -3, -5 and -6, Phenotypic characterization of BMSC by RT-PCR showed transcripts of the fat marker adipsin and the prechondrocytic marker procollagen type IIA; however, we were unable to detect the mature cartilage markers, procollagen type IIB and aggrecan, even after growth factor treatment. Our data indicate that CDMP-1, CDMP-2, BMP-6 and OP-l enhance the osteogenic phenotype in BMSC, with CDMPs being clearly less osteogenic than BMPs, The endogenous expression of a variety of CDMPs/BMPs and their respective ALK receptors, suggests a possible involvement of these growth factors in the osteogenic differentiation of bone marrow progenitor cells, (C) 2000 Academic Press.