Gruber R, Mayer C, Schulz W, Graninger W, Peterlik M, Watzek G, Luyten F P, Erlacher L
Department of Rheumatology, Clinic of Internal Medicine III, Austria.
Cytokine. 2000 Nov;12(11):1630-8. doi: 10.1006/cyto.2000.0760.
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-1) 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-1 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.
软骨衍生形态发生蛋白1和2（CDMP - 1和CDMP - 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。在整个成年期，骨髓来源的前体细胞保持着响应局部生长因子而分化为成骨细胞的能力。本研究检测了CDMP - 1、CDMP - 2、BMP - 6和成骨蛋白1（OP - 1）在骨髓基质细胞（BMSC）中的成骨潜力，并研究了CDMPs/BMPs及其各自的激活素受体样激酶（ALK）受体的内源性表达。在无血清条件下，将BMSC暴露于CDMP - 1、CDMP - 2、BMP - 6和OP - 1 4天，通过碱性磷酸酶活性和骨钙素合成评估，以剂量依赖方式刺激了成骨谱系的进展。与BMPs相比，经Northern印迹分析证实，CDMP - 1尤其是CDMP - 2的成骨能力明显较弱。此外，BMSC被证明内源性表达CDMP - 2、BMP - 2至 - 6以及ALK - 1、 - 2、 - 3、 - 5和 - 6。通过RT - PCR对BMSC进行表型特征分析显示有脂肪标志物脂联素和前软骨细胞标志物IIA型前胶原的转录本；然而，即使在生长因子处理后，我们也未能检测到成熟软骨标志物IIB型前胶原和聚集蛋白聚糖。我们的数据表明，CDMP - 1、CDMP - 2、BMP - 6和OP - 1增强了BMSC中的成骨表型，其中CDMPs的成骨能力明显低于BMPs。多种CDMPs/BMPs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。
