title: Synthetic osteogenic growth peptide promotes differentiation of human bone marrow mesenchymal stem cells to osteoblasts via RhoA/ROCK pathway.
abstract: The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide that has attracted considerable clinical interest as a bone anabolic agent and hematopoietic stimulator. In vitro studies have demonstrated that OGP directly regulates the bone marrow mesenchymal stem cells' (BMSCs) differentiation into osteoblasts. However, the exact mechanism of this process remains unknown. In the present study, we investigated the role of RhoA/ROCK signaling in differentiation along this lineage using human BMSCs. OGP treatment increased the mRNA level of bone morphogenetic protein-2 and alkaline phosphatase activity after osteogenic induction. Analysis of BMSCs induced in the presence of OGP revealed an increase in RhoA activity, and phosphorylation of FAK and cofilin. The ROCK-specific inhibitors, Y27632, blocked the OGP-induced regulation of BMSC differentiation. Taken together, these data suggest that OGP not only acts on BMSCs to stimulate osteogenic differentiation, but also in a dose-dependent manner, and this effect is mediated via the activation of RhoA/ROCK pathway.
authors: Department of Orthopedics Surgery, Shanghai Zhongshan Hospital, Fudan University, Shanghai 200032, People's Republic of China.
authors: Zixian
authors: Z
authors: Chen
authors: Xiaofeng
authors: X
authors: Wang
authors: Yunchao
authors: Y
authors: Shao
authors: Deyuan
authors: D
authors: Shi
authors: Tongyi
authors: T
authors: Chen
authors: Dafu
authors: D
authors: Cui
authors: Xiaoxing
authors: X
authors: Jiang
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000328:Adult; D000577:Amides / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006657:Histones / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000577:Amides; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D011725:Pyridines; C074533:osteogenic growth peptide; C108830:Y 27632; D019000:Phosphotyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein