Molecular events caused by mechanical stress in bone

Shintaro Nomura, Teruko Takano-Yamamoto

Research output: Contribution to journalShort surveypeer-review

218 Citations (Scopus)


The shape of bone changes as a result of bone remodeling corresponding to physical circumstances such as mechanical stress. The tissue which receives the loaded mechanical stress most efficiently is bone matrix. Recent studies revealed the function of osteocytes as mechanosensors in the early stage of bone remodeling. Loaded mechanical stress is converted to a series of biochemical reactions, and finally activates osteoclasts and osteoblasts to cause bone resorption and formation. Biochemical and molecular biological studies have recently resulted in the identification of the gene of which expression level is changed by mechanical stress. Nitric oxide (NO) and cAMP is secreted in response to mechanical stress in the immediate early stage. Genes encoding enzymes such as glutamate/aspartate transporter (GLAST), nitric oxide synthetase (NOS) and prostaglandin G/H synthetase (PGHS-2) are identified as mechanical stress-responsive. The expression level of IGF-I is enhanced under the control of PTH/PTHrP. The expression of c-fos is increased by loading of mechanical stress. AP1, a heterodimer of c-FOS/c-JUN, functions as a transcription factor of downstream gene(s). Elements including AP1 sites, cyclic AMP response elements (CRE) and shear stress response elements (SSRE) are found in the promoter region of mechanical stress-response genes. The enhanced expression of osteopontin (OPN) in the osteocytes of bone resorption sites was demonstrated by in situ hybridization and immunohistochemistry and transdifferentiation of chondrocytes with the abundant expression of BMP-2 and -4 in the process of distraction osteogenesis was observed. (C) 2000 Elsevier Science B.V./International Society of Matrix Biology.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalMatrix Biology
Issue number2
Publication statusPublished - 2000 May 1
Externally publishedYes


  • Bone remodeling
  • Mechanical stress
  • Osteoclast
  • Osteocytes
  • Osteopontin

ASJC Scopus subject areas

  • Molecular Biology


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