New stress complex receotor system regulates bone mass

• Project/Area Number: 25670639
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NODA Masaki 東京医科歯科大学, 難治疾患研究所, 教授 (50231725)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ストレス / アドレナリン受容体 / PTH / 骨芽細胞 / 破骨細胞 / 骨量

Outline of Final Research Achievements

The molecular basis of bone mass regulation is still incompletely understood. Sympathetic tone acts via beta2 adrenergic receptors in bone and regulates the mass of bone which is the target organ of parathyroid hormone (PTH). However, whether beta2 adrenergic receptor is regulated by PTH in bone cells is not known. We therefore investigated the effects of PTH on beta2 adrenergic receptor gene expression in osteoblast-like MC3T3-E1 cells. PTH treatment immediately suppressed the expression levels of beta2 adrenergic receptor mRNA. This PTH effect was dose-dependent starting as low as 1 nM. PTH action on beta2 adrenergic receptor gene expression was inhibited by a transcriptional inhibitor, DRB, but not by a protein synthesis inhibitor, cycloheximide suggesting direct transcription control. Knockdown of beta2 adrenergic receptor promoted PTH-induced expression of c-fos, an immediate early response gene.

Research Products

• [Journal Article] Stability of mRNA influences steoporotic bone mass via CNOT3 (2014)
  • Author(s): Watanabe, C. Morita, M. Yamamoto T. (13名)
  • Journal Title: Natl Acad Sci U S A Volume: Vol.111 Issue: 7 Pages: 2692-2697
  • DOI: 10.1073/pnas.1316932111
  • Peer Reviewed / Open Access
• [Journal Article] Migration linked to FUCCI-indicated cell cycle is controlled by PTH and mechanical stress† (2014)
  • Author(s): Shirakawa J, Ezura Y, Moriya S, Kawasaki M, Yamada T, Notomi T, Nakamoto T, Hayata T, Miyawaki A, Omura K, Noda M.
  • Journal Title: Journal of Cellular Physiology Volume: - Issue: 10 Pages: 1353-8
  • DOI: 10.1002/jcp.24605
  • Peer Reviewed / Open Access
• [Journal Article] Hindlimb-Unloading Suppresses B-cell Population in The Bone Marrow and Peripheral Circulation Associated with OPN Expression in Circulating Blood Cells (2014)
  • Author(s): Ezura Y, Nagata J, Nagao M, Hemmi H, Hayata T, Rittling S, Denhardt DT, Noda M.
  • Journal Title: Journal of Bone and Mineral Metabolism Volume: -
  • Peer Reviewed