Journal of Cell Communication and Signaling

, Volume 6, Issue 4, pp 225–232 | Cite as

Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress

  • Tadashi Honjo
  • Satoshi Kubota
  • Hiroshi Kamioka
  • Yasuyo Sugawara
  • Yoshihito Ishihara
  • Takashi Yamashiro
  • Masaharu Takigawa
  • Teruko Takano-YamamotoEmail author
Research Article


Fluid flow stress (FSS) is a major mechanical stress that induces bone remodeling upon orthodontic tooth movement, whereas CCN family protein 2 (CCN2) is a potent regenerator of bone defects. In this study, we initially evaluated the effect of laminar FSS on Ccn2 expression and investigated its mechanism in osteoblastic MC3T3-E1 cells. The Ccn2 expression was drastically induced by uniform FSS in an intensity dependent manner. Of note, the observed effect was inhibited by a Rho kinase inhibitor Y27632. Moreover, the inhibition of actin polymerization blocked the FSS-induced activation of Ccn2, whereas inducing F-actin formation using cytochalasin D and jasplakinolide enhanced Ccn2 expression in the same cells. Finally, F-actin formation was found to induce osteoblastic differentiation. In addition, activation of cyclic AMP-dependent kinase, which inhibits Rho signaling, abolished the effect of FSS. Collectively, these findings indicate the critical role of actin polymerization and Rho signaling in CCN2 induction and bone remodeling provoked by FSS.


Osteoblasts Connective tissue growth factor CTGF CCN2 Fluid shear stress Actin polymerization 



We thank Dr. M. Miyamoto for providing technical assistance in designing and completing the real time PCR protocols. This study was supported in part by grants-in-aid (20249081T.T-Y) for scientific research from the Japan Society for the Promotion of Science.


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Copyright information

© The International CCN Society 2012

Authors and Affiliations

  • Tadashi Honjo
    • 1
  • Satoshi Kubota
    • 2
  • Hiroshi Kamioka
    • 1
  • Yasuyo Sugawara
    • 1
  • Yoshihito Ishihara
    • 1
  • Takashi Yamashiro
    • 1
  • Masaharu Takigawa
    • 2
  • Teruko Takano-Yamamoto
    • 3
    Email author
  1. 1.Department of OrthodonticsOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  2. 2.Department of Biochemistry and Molecular DentistryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Department of Orthodontics and Dentofacial OrthopedicsTohoku University Graduate School of DentistrySendaiJapan

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