Rho-kinase negatively regulates thyroid hormone-stimulated osteocalcin synthesis in osteoblasts

Akira Kondo1, Haruhiko Tokuda, Kenji Kato

  • 1Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.

Biochimie
|November 6, 2012
PubMed

Insights

Triiodothyronine (T3) activates Rho-kinase in osteoblasts, which inhibits osteocalcin synthesis. Inhibiting Rho-kinase enhances T3-induced osteocalcin release and gene expression, revealing a novel regulatory pathway in bone metabolism.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Rho-associated kinase (Rho-kinase) is implicated in vascular smooth muscle contraction and cellular functions, including bone metabolism.
  • Triiodothyronine (T3) is a thyroid hormone known to influence various cellular processes.

Purpose of the Study:

  • To investigate the role of Rho-kinase in triiodothyronine (T3)-induced osteocalcin synthesis in osteoblast-like MC3T3-E1 cells.
  • To elucidate the regulatory mechanism of Rho-kinase in T3-mediated bone metabolism.

Main Methods:

  • MC3T3-E1 cells were treated with T3, and Rho-kinase activity was assessed by MYPT-1 phosphorylation.
  • Specific Rho-kinase inhibitors (Y27632, fasudil) and Rho A-siRNA were used to evaluate their effects on osteocalcin synthesis.
  • Osteocalcin release and mRNA expression levels were measured.

Main Results:

  • T3 induced time-dependent phosphorylation of MYPT-1, a Rho-kinase substrate.
  • Rho-kinase inhibitors (Y27632, fasudil) attenuated T3-induced MYPT-1 phosphorylation.
  • Inhibition of Rho-kinase significantly enhanced T3-stimulated osteocalcin release and mRNA expression.
  • Rho-knockdown cells showed augmented T3-stimulated osteocalcin release.

Conclusions:

  • T3 activates Rho-kinase in osteoblasts.
  • Rho-kinase acts as a negative regulator of T3-stimulated osteocalcin synthesis.
  • These findings reveal a novel regulatory role for Rho-kinase in thyroid hormone-mediated bone metabolism.

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