<b>Tensile stress stimulates the expression of osteogenic cytokines/growth factors and matricellular proteins in the mouse cranial suture at the site of osteoblast differ</b><b>entiation </b>

Abstract

Mechanical stress promotes osteoblast proliferation and differentiation from mesenchymal stem cells (MSCs). Although numerous growth factors and cytokines are known to regulate this process, information regarding the differentiation of mechanically stimulated osteoblasts from MSCs in in vivo microenvironment is limited. To determine the significant factors involved in this process, we performed a global analysis of differentially expressed genes, in response to tensile stress, in the mouse cranial suture wherein osteoblasts differentiate from MSCs. We found that the gene expression levels of several components involved in bone morphogenetic protein, Wnt, and epithelial growth factor signalings were elevated with tensile stress. Moreover gene expression of some extracellular matrices (ECMs), such as cysteine rich protein 61 (Cyr61)/CCN1 and galectin-9, were upregulated. These ECMs have the ability to modulate the activities of cytokines and are known as matricellular proteins. Cyr61/CCN1 expression was prominently increased in the fibroblastic cells and preosteoblasts in the suture. Thus, for the first time we demonstrated the mechanical stimulation of Cyr61/CCN1 expression in osteogenic cells in an ex vivo system. These results suggest the importance of matricellular proteins along with the cytokine-mediated signaling for the mechanical regulation of MSC proliferation and differentiation into osteoblastic cell lineage in vivo.Mechanical stress controls bone mass by affecting recruitment of osteoprogenitors as well as osteoblast differentiation from mesenchymal stem cells (MSCs) in the bone tissue (7,8). Elucidation of the precise mechanisms involved in the osteoblastogenesis stimulated by mechanical stress, especially the mechanism for osteogenic differentiation of MSCs, will contribute to the progress of regenerative medicine for effective production of bone tissue from MSC sources. Increasing evidence has revealed that the process of mechanical stress-stimulated osteoblastogenesis is controlled by many cytokines/growth factors (9,32,34,36). Especially bone morphogenetic protein (BMP) signaling and Wnt signaling play important roles in the development of osteoblasts from MSCs (5), but the more relevant factors among these or

The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation

“…Galectin-9 expression is also upregulated in MSCs undergoing stress-induced osteoblast differentiation. A 1.6-fold increase in galectin-9 mRNA was reported at 3 h upon tensile stress applied to parietal mouse bones along with bone morphogenetic proteins, Wnt, epithelial growth factor signaling factors, and matricellular proteins [ 60 ]. Similarly, the expression of galectin-9 was increased in human MSCs cells during TGFβ3-induced differentiation into chondrocytes and recombinant galectin-9 at a concentration of 1–100 nM enhanced this differentiation through up-regulation of Smad2 signaling [ 41 ].…”

Expression of Non-collagenous Bone Matrix Proteins in Osteoblasts Stimulated by Mechanical Stretching in the Cranial Suture of Neonatal Mice

“…The organ culture system with stretching stimulus using coiled springs has been described previously. 18,19 Briefly, the left and right parietal bones of 4-day-old ddY mice were excised, with presenting the intact sagittal suture. In the stretched experimental groups (EXP), these parietal bones were then affixed to an activated coiled spring, creating a continuous stretching stimulus in the direction of enlarging the suture.…”

Extracellular Matrix in Human Craniofacial Development

“…Turning to the cranium, pressure gradients caused by brain enlargement deform the ECM of the dura mater, creating tensile forces that are then transmitted to the bones and sutures of the cranium (Moazen et al 2016; Marghoub et al 2018). This increase in suture tension stimulates several biochemical signaling processes (e.g., growth factor and BMP signaling; Ikegame et al 2016) in the suture mesenchyme that lead to cell proliferation, differentiation, and suture fusion. Indeed, abnormally reduced intracranial pressure and the associated reduction in cranial-ECM tension can result in premature suture fusion (craniosynostosis) and resulting microcephaly (Park and Yoon 2017).…”