Mechanotransduction in Bone Cells: Induction of Nitric Oxide and Prostaglandin Synthesis by Fluid Shear Stress, but Not by Mechanical Strain

  • Rolf Smalt
  • Fred T. Mitchell
  • Ron L. Howard
  • Timothy J. Chambers
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 433)


The skeleton acts as a support for the rest of the body, and it has long been known that bone tissue adapts to its local mechanical environment: mechanical loading leads to an increase in the bone mass and density, whereas disuse results in a net loss of bone. It has been found that bones respond primarily to dynamic rather that static loads1. Mechanical loading of bone cells is associated with increased prostaglandin E2 (PGE2) production2, and inhibition of prostaglandin synthesis suppresses the osteogenic response3. Inhibition of nitric oxide synthase (NOS) also abolishes the loading response, indicating that nitric oxide (NO) production has an essential early role in bone remodeling, too4.


Nitric Oxide Fluid Flow Bone Cell Osteoblastic Cell Mechanical Strain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    L.E. Lanyon and C.T. Rubin, Static vs dynamic loads as an influence on bone remodelling, J. Biomechs. 17: 897 (1984).CrossRefGoogle Scholar
  2. 2.
    I. Binderman, U. Zor, A.M. Kaye, Z. Shimshoni, A. Harell and D. Somjen, The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2. Calcif. Tissue Int. 42: 261 (1988).PubMedCrossRefGoogle Scholar
  3. 3.
    M.J. Pead and L.E. Lanyon, Indomethacin modulation of load-related stimulation of new bone formation in vivo, Calcif. Tissue Int. 45: 34 (1989).PubMedCrossRefGoogle Scholar
  4. 4.
    S.W. Fox, T.J. Chambers and J.W.M. Chow, Nitric oxide is an early mediator of the increase in bone formation by mechanical stimulation, Am. J. Physiol. 270: E955 (1996).PubMedGoogle Scholar
  5. 5.
    M.J. Kuchan and J.A. Frangos, Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells, Am. J. Physiol. 266: C628 (1994).PubMedGoogle Scholar
  6. 6.
    K.M. Reich and J.A. Frangos, Effect of flow on prostaglandin E2 and inositol triphosphate levels in osteoblasts, Am. J. Physiol. 261: C428 (1991).PubMedGoogle Scholar
  7. 7.
    B.M. Jaffe and H.R. Behrman, Prostaglandins and prostaglandin metabolites, in: Methods of Hormone Radioimmunoassay. B.M. Jaffe and H.R. Behrman eds., Academic Press, New York (1974).Google Scholar
  8. 8.
    K. Shibuki, An electrochemical microprobe for detecting nitric oxide release in brain tissue, Neuroscl. Res. 9: 69 (1990).CrossRefGoogle Scholar
  9. 9.
    L.V. McIntire and S.G. Eskin, Mechanical and biochemical aspects of leukocyte interactions with model vessel walls, KROC Foundation Series 16: 209 (1984).PubMedGoogle Scholar
  10. 10.
    C.H. Turner, M.R. Forwood and M.W. Otter, Mechanotransduction in bone: do bone cells act as sensors of fluid flow?, FASEB J. 8: 875 (1994).PubMedGoogle Scholar
  11. U.S. Weinbaum, S.C. Cowin and Y. Zeng, A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses, J. Biomechs. 27: 339 (1994).CrossRefGoogle Scholar
  12. 12.
    J. Klein-Nulend, A. Van der Plas, C.M. Semeins, N.E. Ajubi, J.A. Frangos, P.J. Nijweide and E.H. Burger, Sensitivity of osteocytes to biomechanical stress in vitro, FASEB J. 9: 441 (1995).PubMedGoogle Scholar
  13. 13.
    D.L. Johnson, T.N. McAllister and J.A. Frangos, Fluid-flow stimulates rapid and continuous release of nitric oxide in osteoblasts, Am. J. Physiol. 34: E205 (1996).Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Rolf Smalt
    • 1
  • Fred T. Mitchell
    • 2
  • Ron L. Howard
    • 2
  • Timothy J. Chambers
    • 1
  1. 1.Histopathology DepartmentSt. George’s Hospital Medical SchoolLondonUK
  2. 2.Medical Physics DepartmentAtkinson Morley’s HospitalLondonUK

Personalised recommendations