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.

Sphingosine-1-phosphate/S1PR2-mediated signaling triggers Smad1/5/8 phosphorylation and thereby induces Runx2 expression in osteoblasts

“…Gi-independent S1P/S1PR2 signaling also activates RhoA/Rho kinase (ROCK) in smooth muscle cells and CHO cells [19,20]. Interestingly, the RhoA/ROCK signaling pathway regulates both cytoskeletal dynamics [21] and osteoblast differentiation [22,23]. However, whether S1P/S1PR2-mediated signaling-including S1PR2-mediated RhoA/ROCK signaling-plays a role in osteoblast differentiation is unknown.…”

Effects of Combined Treatment with Complex S. typhimurium Antigens and Factors Stimulating Osteogenesis (Curettage, BMP-2) on Multipotent Bone Marrow Stromal Cells and Serum Concentration of Cytokines in CBA Mice

“…Tibial curettage and administration of BMP-2 to animals were used as osteogenesis-inducing stimuli. Curettage is an adequate model for investigation of the mechanisms of post-traumatic regeneration of the bone tissue: it induces systemic increase in MSC level [4] and their osteogenic activity due to growth factors release into circulation [5]. BMP-2 induces a cascade response leading to chondrogenesis, osteogenesis, angiogenesis, and controlled synthesis of the extracellular matrix [14].…”

Dimethyloxalylglycine Promotes Bone Marrow Mesenchymal Stem Cell Osteogenesis via Rho/ROCK Signaling

“…Previous studies showed that RhoA/ROCK signaling played a key role in the regulation of osteogenesis [16][17][18]. Results showed that after 24 h of culture, 0.5 mM DMOG increased the expression of GTP-bound RhoA (P < 0.001 vs. control group).…”

“…Indeed, Wang et al [16] reported that bone morphogenic protein (BMP) promotes human mesenchymal stem cell (MSC) osteogenesis by altering cytoskeleton via activation of RhoA/ROCK signaling. Other studies showed that osteogenic growth peptide (OGP) [17], connective tissue growth factor [18], extracellular matrix [19], and hydrostatic pressure [20] promote the osteogenic differentiation of human bone marrow MSC (BMSC) via RhoA/ROCK signaling activation.…”