Mechanical Stress and Bone

  • Masaki Noda
  • Tadayoshi Hayata
  • Tetsuya Nakamoto
  • Takuya Notomi
  • Yoichi Ezura


Bone has been known to adapt to mechanical stress (Amin 2010; Beier and Loeser 2010; Currey 2010; Temiyasathit and Jacobs 2010). The presence of mechanical stress increases bone mass and the absence of mechanical stress reduces bone mass. Bending of weight-bearing long bone increases pressure on the concave side and decreases it on the convex side. Under such circumstances, bone is accumulated on the concave side and is reduced on the convex side. This can be seen after angular deformity due to malunion of fractures in children where minor angular deformity could be corrected during the growth of the children.


Bone Resorption Bone Marrow Cell Bone Formation Rate Mineral Apposition Rate Osteoclast Surface 
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.


  1. Amin S (2010) Mechanical factors and bone health: effects of weightlessness and neurologic injury. Curr Rheumatol Rep 12  :  170–176PubMedCrossRefGoogle Scholar
  2. Beier F, Loeser RF (2010) Biology and pathology of Rho GTPase, PI-3 kinase-Akt, and MAP kinase signaling pathways in chondrocytes. J Cell Biochem 110  :  573–580PubMedCrossRefGoogle Scholar
  3. Calvi LM, Sims NA, Hunzelman JL, Knight MC, Giovannetti A, Saxton JM, Kronenberg HM, Baron R, Schipani E (2001) Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone. J Clin Invest 107  :  277–286PubMedCrossRefGoogle Scholar
  4. Chung CJ, Soma K, Rittling SR, Denhardt DT, Hayata T, Nakashima K, Ezura Y, Noda M (2008) OPN deficiency suppresses appearance of odontoclastic cells and resorption of the tooth root induced by experimental force application. J Cell Physiol 214  :  614–620PubMedCrossRefGoogle Scholar
  5. Currey JD (2010) Mechanical properties and adaptations of some less familiar bony tissues. J Mech Behav Biomed Mater 3  :  357–372PubMedCrossRefGoogle Scholar
  6. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G (2005) Sympathetic regulation of osteoclastogenesis is required for gonadectomy-induced bone loss and antagonized by CART. Nature 433  :  7028Google Scholar
  7. Goodship AE, Cunningham JL, Oganov V, Darling J, Miles AW, Owen GW (1998) Bone loss during long term space flight is prevented by the application of a short term impulsive mechanical stimulus. Acta Astronaut 43  :  65–75PubMedCrossRefGoogle Scholar
  8. Guilak F, Leddy HA, Liedtke W (2010) Transient receptor potential vanilloid 4: the sixth sense of the musculoskeletal system. Ann NY Acad Sci 1192  :  404–409PubMedCrossRefGoogle Scholar
  9. Hino K, Nifuji A, Morinobu M, Tsuji K, Ezura Y, Nakashima K, Yamamoto H, Noda M (2006) Unloading-induced bone loss was suppressed in gold-thioglucose treated mice. J Cell Biochem 99  :  845–852PubMedCrossRefGoogle Scholar
  10. Ishijima M, Rittling SR, Yamashita T, Tsuji K, Kurosawa H, Nifuji A, Denhardt DT, Noda M (2001) Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin. J Exp Med 193  :  399–404PubMedCrossRefGoogle Scholar
  11. Ishijima M, Tsuji K, Rittling SR, Yamashita T, Kurosawa H, David TD, Nifuji A, Noda M (2002) Resistance to unloading-induced three-dimensional bone loss in osteopontin-deficient mice. J Bone Miner Res 17  :  661–667PubMedCrossRefGoogle Scholar
  12. Ishijima M, Ezura Y, Tsuji K, Rittling SR, Kurosawa K, Denhardt DT, Emi M, Nifuji A, Noda M (2006) Osteopontin is associated with nuclear factor κB gene expression during tail-suspension-induced bone loss. Exp Cell Res 312  :  3075–3083PubMedCrossRefGoogle Scholar
  13. Ishijima M, Tsuji K, Rittling SR, Yamashita T, Kurosawa H, Denhardt DT, Nifuji A, Ezura Y, Noda M (2007) Osteopontin is required for mechanical stress-dependent signals to bone marrow cells. J Endocrinol 193  :  236–243CrossRefGoogle Scholar
  14. Kirsch K, Kensinger M, Hanafusa H, August A (2002) A p130Cas tyrosine phosphorylated substrate domain decoy disrupts v-crk signaling. BMC Cell Biol 3  :  18PubMedCrossRefGoogle Scholar
  15. Komori T (2010) Regulation of osteoblast differentiation by runx2. Adv Exp Med Biol 658  :  43–49PubMedCrossRefGoogle Scholar
  16. Kondo H, Nifuji A, Takeda S, Ezura Y, Rittling S, Denhardt DT, Nakashima K, Karsenty G, Noda M (2005) Unloading induces osteoblastic cell suppression and osteoclastic cell activation to lead to bone loss via sympathetic nervous system. J Biol Chem 280  :  30192–30200PubMedCrossRefGoogle Scholar
  17. Kontulainen S, Sievänen H, Kannus P, Pasanen M, Vuori I (2002) Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls. J Bone Miner Res 17  :  2281–2289PubMedCrossRefGoogle Scholar
  18. Lorenzo IM, Liedtke W, Sanderson MJ, Valverde MA (2008) TRPV4 channel participates in receptor-operated calcium entry and ciliary beat frequency regulation in mouse airway epithelial cells. Proc Natl Acad Sci USA 105  :  12611–12616PubMedCrossRefGoogle Scholar
  19. Lou Y, Javed A, Hussain S, Colby J, Frederick D, Pratap J, Xie R, Gaur T, van Wijnen AJ, Jones SN, Stein GS, Lian JB, Stein JL (2009) A Runx2 threshold for the cleidocranial dysplasia phenotype. Hum Mol Genet 18  :  556–568PubMedCrossRefGoogle Scholar
  20. Masuyama R, Vriens J, Voets T, Karashima Y, Owsianik G, Vennekens R, Lieben L, Torrekens S, Moermans K, Vanden Bosch A, Bouillon R, Nilius B, Carmeliet G (2008) TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metab 8  :  257–265PubMedCrossRefGoogle Scholar
  21. Mendoza SA, Fang J, Gutterman DD, Wilcox DA, Bubolz AH, Li R, Suzuki M, Zhang DX (2010) TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress. Am J Physiol Heart Circ Physiol 298  :  466–476CrossRefGoogle Scholar
  22. Mizoguchi F, Mizuno A, Hayata T, Nakashima K, Heller S, Ushida T, Sokabe M, Miyasaka N, Suzuki M, Ezura Y, Noda M (2008) Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss. J Cell Physiol 216  :  47–53PubMedCrossRefGoogle Scholar
  23. Mizuno A, Matsumoto N, Imai M, Suzuki M (2003) Impaired osmotic sensation in mice lacking TRPV4. Am J Physiol Cell Physiol 285(1)  :  C96–C101Google Scholar
  24. Morinobu M, Ishijima M, Rittling SR, Tsuji K, Yamamoto H, Nifuji A, Denhardt DT, Noda M (2003) Osteopontin expression in osteoblasts and osteocytes during bone formation under mechanical stress in the calvarial suture in vivo. J Bone Miner Res 18  :  1706–1715PubMedCrossRefGoogle Scholar
  25. Nakamoto T, Yamagata T, Sakai R, Ogawa S, Honda H, Ueno H, Hirano N, Yazaki Y, Hirai H (2000) CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases. Mol Cell Biol 20  :  1649–1658PubMedCrossRefGoogle Scholar
  26. Ono N, Nakashima K, Schipani E, Hayata T, Ezura Y, Soma K, Kronenberg HM, Noda M (2007) Constitutively active parathyroid hormone receptor signaling in cells in osteoblastic lineage suppresses mechanical unloading-induced bone resorption. J Biol Chem 282  :  25509–25516PubMedCrossRefGoogle Scholar
  27. Paszek MJ, Boettiger D, Weaver VM, Hammer DA (2009) Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput Biol 5  :  e1000604PubMedCrossRefGoogle Scholar
  28. Pineda B, Hermenegildo C, Laporta P, Tarín JJ, Cano A, García-Pérez MA (2010) Common polymorphisms rather than rare genetic variants of the Runx2 gene are associated with femoral neck BMD in Spanish women. J Bone Miner Metab. doi: 10.1007/s00774-010-0183-2Google Scholar
  29. Rios HF, Ma D, Xie Y, Giannobile WV, Bonewald LF, Conway SJ, Feng JQ (2008) Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice. J Periodontol 79  :  1480–1490PubMedCrossRefGoogle Scholar
  30. Sakai A, Sakata T, Tanaka S, Okazaki R, Kunugita N, Norimura T, Nakamura T (2002) Disruption of the p53 gene results in preserved trabecular bone mass and bone formation after mechanical unloading. J Bone Miner Res 17  :  119–127PubMedCrossRefGoogle Scholar
  31. Salingcarnboriboon R, Tsuji K, Komori T, Nakashima K, Ezura Y, Noda M (2006) Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo. Endocrinology 147  :  2296–2305PubMedCrossRefGoogle Scholar
  32. Sawada Y, Tamada M, Dubin-Thaler BJ, Cherniavskaya O, Sakai R, Tanaka S, Sheetz MP (2006) Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell 127  :  1015–1026PubMedCrossRefGoogle Scholar
  33. Sokabe T, Fukumi-Tominaga T, Yonemura S, Mizuno A, Tominaga M (2010) The TRPV4 channel contributes to intercellular junction formation in keratinocytes. J Biol Chem 285  :  18749–18758PubMedCrossRefGoogle Scholar
  34. Son AR, Yang YM, Hong JH, Lee SI, Shibukawa Y, Shin DM (2009) Odontoblast TRP channels and thermo/mechanical transmission. J Dent Res 88  :  1014–1019PubMedCrossRefGoogle Scholar
  35. Suzuki M, Hirao A, Mizuno A (2003a) Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4). J Biol Chem 278(51)  :  51448–51453. Epub 2003 Sep 28. Erratum in: J Biol Chem 2005: 280(27)  :  25948Google Scholar
  36. Suzuki M, Watanabe Y, Oyama Y, Mizuno A, Kusano E, Hirao A, Ookawara S (2003b) Localization of mechanosensitive channel TRPV4 in mouse skin. Neurosci Lett 353(3)  :  189–192Google Scholar
  37. Suzuki M, Mizuno A, Kodaira K, Imai M (2003c) Impaired pressure sensation in mine lacking TRPV4. J Biol Chem 278(25)  :  22664–22668Google Scholar
  38. Tamada M, Sheetz MP, Sawada Y (2004) Activation of a signaling cascade by cytoskeleton stretch. Dev Cell 7  :  709–718PubMedCrossRefGoogle Scholar
  39. Temiyasathit S, Jacobs CR (2010) Osteocyte primary cilium and its role in bone mechanotransduction. Ann NY Acad Sci 1192  :  422–428PubMedCrossRefGoogle Scholar
  40. Thodeti CK, Matthews B, Ravi A, Mammoto A, Ghosh K, Bracha AL, Ingber DE (2009) TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ Res 104  :  1123–1130PubMedCrossRefGoogle Scholar
  41. Yu V, Damek-Poprawa M, Nicoll SB, Akintoye SO (2009) Dynamic hydrostatic pressure promotes differentiation of human dental pulp stem cells. Biochem Biophys Res Commun 386  :  661–665PubMedCrossRefGoogle Scholar
  42. Ziegler N, Alonso A, Steinberg T, Woodnutt D, Kohl A, Müssig E, Schulz S, Tomakidi P (2010) Mechano-transduction in periodontal ligament cells identifies activated states of MAP-kinases p42/44 and p38-stress kinase as a mechanism for MMP-13 expression. BMC Cell Biol 11  :  10PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Masaki Noda
    • 1
  • Tadayoshi Hayata
    • 1
  • Tetsuya Nakamoto
    • 1
  • Takuya Notomi
    • 1
  • Yoichi Ezura
    • 1
  1. 1.Department of Molecular Pharmacology, Division of Advanced Molecular Medicine, Medical Research InstituteTokyo Medical and Dental UniversityBunkyo-kuJapan

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