<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>

  • IKEGAME Mika
    Department of Oral Morphology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School
  • TABUCHI Yoshiaki
    Division of Molecular Genetics, Life Science Research Center, University of Toyama
  • FURUSAWA Yukihiro
    Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
  • KAWAI Mariko
    Department of Oral Morphology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Department of Pharma-cology, Osaka Dental University
  • HATTORI Atsuhiko
    College of Liberal Arts and Sciences, Tokyo Medical and Dental University
  • KONDO Takashi
    Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
  • YAMAMOTO Toshio
    Department of Oral Morphology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

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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.

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