Skip to main content

Advertisement

Log in

Mechanotransduction in Human Bone

In Vitro Cellular Physiology that Underpins Bone Changes with Exercise

  • Review Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

Bone has a remarkable ability to adjust its mass and architecture in response to a wide range of loads, from low-level gravitational forces to high-level impacts. A variety of types and magnitudes of mechanical stimuli have been shown to influence human bone cell metabolism in vitro, including fluid shear, tensile and compressive strain, altered gravity and vibration. Therefore, the current article aims to synthesize in vitro data regarding the cellular mechanisms underlying the response of human bone cells to mechanical loading. Current data demonstrate commonalities in response to different types of mechanical stimuli on the one hand, along with differential activation of intracellular signalling on the other. A major unanswered question is, how do bone cells sense and distinguish between different types of load? The studies included in the present article suggest that the type and magnitude of loading may be discriminated by overlapping mechanosensory mechanisms including (i) ion channels; (ii) integrins; (iii) G-proteins; and (iv) the cytoskeleton. The downstream signalling pathways identified to date appear to overlap with known growth factor and hormone signals, providing a mechanism of interaction between systemic influences and the local mechanical environment. Finally, the data suggest that exercise should emphasize the amount of load rather than the number of repetitions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1

Similar content being viewed by others

References

  1. Rittweger J, Frost HM, Schiessl H, et al. Muscle atrophy and bone loss after 90 days’ bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study. Bone 2005; 36: 1019–29

    PubMed  Google Scholar 

  2. Giangregorio L, Mc Cartney N. Bone loss and muscle atrophy in spinal cord injury: epidemiology, fracture prediction, and rehabilitation strategies. J Spinal Cord Med 2006; 29: 489–500

    PubMed  Google Scholar 

  3. Jones DB, Scholuebbers G, Matthias HH. Wolff’s law, piezoelectricity and mechanical responses in the skeleton. Proceedings of the Annual International Conference of the IEEE; 1988 Nov 4-7; New Orleans (LA)

    Google Scholar 

  4. Frost HM. Bone’s mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol 2003; 275: 1081–101

    PubMed  Google Scholar 

  5. Tasevski V, Sorbetti JM, Chiu SS, et al. Influence of mechanical and biological signals on gene expression in human MG−63 cells: evidence for a complex interplay between hydrostatic compression and vitamin D3 or TGF—beta1 on MMP−1 and MMP−3 mRNA levels. Biochem Cell Biol 2005; 83: 96–107

    PubMed  CAS  Google Scholar 

  6. Cheng MZ, Rawlinson SC, Pitsillides AA, et al. Human osteoblasts’ proliferative responses to strain and 17beta—estradiol are mediated by the estrogen receptor and the receptor for insulin—like growth factor I. J Bone Miner Res 2002; 17: 593–602

    PubMed  CAS  Google Scholar 

  7. Sorkin AM, Dee KC, Knothe Tate ML. ‘Culture shock’ from the bone cell’s perspective: emulating physiological conditions for mechanobiological investigations. Am J Physiol Cell Physiol 2004; 287: C1527–36

    Google Scholar 

  8. Jorgensen NR, Henriksen Z, Brot C, et al. Human osteoblastic cells propagate intercellular calcium signals by two different mechanisms. J Bone Miner Res 2000; 15: 1024–32

    PubMed  CAS  Google Scholar 

  9. Jorgensen NR, Henriksen Z, Sorensen OH, et al. Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors. J Biol Chem 2002; 277: 7574–80

    PubMed  CAS  Google Scholar 

  10. Haut Donahue TL, Genetos DC, Jacobs CR, et al. Annexin V disruption impairs mechanically induced calcium signaling in osteoblastic cells. Bone 2004; 35: 656–63

    PubMed  CAS  Google Scholar 

  11. Li YJ, Batra NN, You L, et al. Oscillatory fluid flow affects human marrow stromal cell proliferation and differentiation. J Orthop Res 2004; 22: 1283–9

    PubMed  CAS  Google Scholar 

  12. Bakker A, Klein-Nulend J, Burger E. Shear stress inhibits while disuse promotes osteocyte apoptosis. Biochem Biophys Res Commun 2004; 320: 1163–8

    PubMed  CAS  Google Scholar 

  13. Taylor AF, Saunders MM, Shingle DL, et al. Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions. Am J Physiol Cell Physiol 2007; 292: C545–52

    Google Scholar 

  14. Liegibel UM, Sommer U, Bundschuh B, et al. Fluid shear of low magnitude increases growth and expression of TGFbeta1 and adhesion molecules in human bone cells in vitro. Exp Clin Endocrinol Diabetes 2004; 112: 356–63

    PubMed  CAS  Google Scholar 

  15. Bakker AD, Klein-Nulend J, Burger EH. Mechanotransduction in bone cells proceeds via activation of COX−2, but not COX−1. Biochem Biophys Res Commun 2003; 305: 677–83

    PubMed  CAS  Google Scholar 

  16. Bannister SR, Lohmann CH, Liu Y, et al. Shear force modulates osteoblast response to surface roughness. J Biomed Mater Res 2002; 60: 167–74

    PubMed  CAS  Google Scholar 

  17. Joldersma M, Burger EH, Semeins CM, et al. Mechanical stress induces COX−2 mRNA expression in bone cells from elderly women. J Biomech 2000; 33: 53–61

    PubMed  CAS  Google Scholar 

  18. Joldersma M, Klein-Nulend J, Oleksik AM, et al. Estrogen enhances mechanical stress—induced prostaglandin production by bone cells from elderly women. Am J Physiol Endocrinol Metab 2001; 280: E436–42

    Google Scholar 

  19. Kapur S, Baylink DJ, Lau KH. Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 2003; 32: 241–51

    PubMed  CAS  Google Scholar 

  20. Klein-Nulend J, Helfrich MH, Sterck JG, et al. Nitric oxide response to shear stress by human bone cell cultures is endothelial nitric oxide synthase dependent. Biochem Biophys Res Commun 1998; 250: 108–14

    PubMed  CAS  Google Scholar 

  21. Mc Donald F, Somasundaram B, Mc Cann TJ, et al. Calcium waves in fluid flow stimulated osteoblasts are G protein mediated. Arch Biochem Biophys 1996; 326: 31–8

    Google Scholar 

  22. Mullender M, El Haj AJ, Yang Y, et al. Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue. Med Biol Eng Comput 2004; 42: 14–21

    PubMed  CAS  Google Scholar 

  23. Ogata T. Increase in epidermal growth factor receptor protein induced in osteoblastic cells after exposure to flow of culture media. Am J Physiol Cell Physiol 2003; 285: C425–32

    Google Scholar 

  24. Pines A, Romanello M, Cesaratto L, et al. Extracellular ATP stimulates the early growth response protein 1 (Egr−1) via a protein kinase C—dependent pathway in the human osteoblastic HOBIT cell line. Biochem J 2003; 373: 815–24

    PubMed  CAS  Google Scholar 

  25. Romanello M, Pani B, Bicego M, et al. Mechanically induced ATP release from human osteoblastic cells. Biochem Biophys Res Commun 2001; 289: 1275–81

    PubMed  CAS  Google Scholar 

  26. Sakai K, Mohtai M, Iwamoto Y. Fluid shear stress increases transforming growth factor beta 1 expression in human osteoblast—like cells: modulation by cation channel blockades. Calcif Tissue Int 1998; 63: 515–20

    PubMed  CAS  Google Scholar 

  27. Sakai K, Mohtai M, Shida J, et al. Fluid shear stress increases interleukin−11 expression in human osteoblast—like cells: its role in osteoclast induction. J Bone Miner Res 1999; 14: 2089–98

    PubMed  CAS  Google Scholar 

  28. Sterck JG, Klein-Nulend J, Lips P, et al. Response of normal and osteoporotic human bone cells to mechanical stress in vitro. Am J Physiol 1998; 274: E1113–20

    Google Scholar 

  29. Weyts FA, Bosmans B, Niesing R, et al. Mechanical control of human osteoblast apoptosis and proliferation in relation to differentiation. Calcif Tissue Int 2003; 72: 505–12

    PubMed  CAS  Google Scholar 

  30. You J, Yellowley CE, Donahue HJ, et al. Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading—induced oscillatory fluid flow. J Biomech Eng 2000; 122: 387–93

    PubMed  CAS  Google Scholar 

  31. Mauney JR, Sjostorm S, Blumberg J, et al. Mechanical stimulation promotes osteogenic differentiation of human bone marrow stromal cells on 3−D partially demineralized bone scaffolds in vitro. Calcif Tissue Int 2004; 74: 458–68

    PubMed  CAS  Google Scholar 

  32. Liu D, Vandahl BB, Birkelund S, et al. Secretion of osteopontin from MG−63 cells under a physiological level of mechanical strain in vitro—a [35S] incorporation approach. Eur J Orthod 2004; 26: 143–9

    PubMed  CAS  Google Scholar 

  33. Carvalho RS, Scott JE, Yen EH. The effects of mechanical stimulation on the distribution of beta 1 integrin and expression of beta 1−integrin mRNA in TE−85 human osteosarcoma cells. Arch Oral Biol 1995; 40: 257–64

    PubMed  CAS  Google Scholar 

  34. Cillo Jr JE, Gassner R, Koepsel RR, et al. Growth factor and cytokine gene expression in mechanically strained human osteoblast—like cells: implications for distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 90: 147–54

    PubMed  Google Scholar 

  35. Di Palma F, Chamson A, Lafage-Proust MH, et al. Physiological strains remodel extracellular matrix and cell—cell adhesion in osteoblastic cells cultured on alumina—coated titanium alloy. Biomaterials 2004; 25: 2565–75

    PubMed  Google Scholar 

  36. Di Palma F, Douet M, Boachon C, et al. Physiological strains induce differentiation in human osteoblasts cultured on orthopaedic biomaterial. Biomaterials 2003; 24: 3139–51

    PubMed  Google Scholar 

  37. Fermor B, Gundle R, Evans M, et al. Primary human osteoblast proliferation and prostaglandin E2 release in response to mechanical strain in vitro. Bone 1998; 22: 637–43

    PubMed  CAS  Google Scholar 

  38. Harter LV, Hruska KA, Duncan RL. Human osteoblast—like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. Endocrinology 1995; 136: 528–35

    PubMed  CAS  Google Scholar 

  39. Jagodzinski M, Drescher M, Zeichen J, et al. Effects of cyclic longitudinal mechanical strain and dexamethasone on osteogenic differentiation of human bone marrow stromal cells. Eur Cell Mater 2004; 7: 35–41; discussion 41

    PubMed  CAS  Google Scholar 

  40. Kaspar D, Seidl W, Neidlinger-Wilke C, et al. Dynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity. J Biomech 2000; 33: 45–51

    PubMed  CAS  Google Scholar 

  41. Kaspar D, Seidl W, Neidlinger-Wilke C, et al. Proliferation of human—derived osteoblast—like cells depends on the cycle number and frequency of uniaxial strain. J Biomech 2002; 35: 873–80

    PubMed  Google Scholar 

  42. Lacouture ME, Schaffer JL, Klickstein LB. A comparison of type I collagen, fibronectin, and vitronectin in supporting adhesion of mechanically strained osteoblasts. J Bone Miner Res 2002; 17: 481–92

    PubMed  CAS  Google Scholar 

  43. Liedert A, Augat P, Ignatius A, et al. Mechanical regulation of HB—GAM expression in bone cells. Biochem Biophys Res Commun 2004; 319: 951–8

    PubMed  CAS  Google Scholar 

  44. Neidlinger-Wilke C, Wilke HJ, Claes L. Cyclic stretching of human osteoblasts affects proliferation and metabolism: a new experimental method and its application. J Orthop Res 1994; 12: 70–8

    PubMed  CAS  Google Scholar 

  45. Neidlinger-Wilke C, Stalla I, Claes L, et al. Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF beta—release in response to cyclic strain. J Biomech 1995; 28: 1411–8

    PubMed  CAS  Google Scholar 

  46. Neidlinger-Wilke C, Grood ES, Wang J-C, et al. Cell alignment is induced by cyclic changes in cell length: studies of cells grown in cyclically stretched substrates. J Orthop Res 2001; 19: 286–93

    PubMed  CAS  Google Scholar 

  47. Peake MA, Cooling LM, Magnay JL, et al. Selected contribution: regulatory pathways involved in mechanical induction of c—fos gene expression in bone cells. J Appl Physiol 2000; 89: 2498–507

    PubMed  CAS  Google Scholar 

  48. Salter DM, Robb JE, Wright MO. Electrophysiological responses of human bone cells to mechanical stimulation: evidence for specific integrin function in mechanotransduction. J Bone Miner Res 1997; 12: 1133–41

    PubMed  CAS  Google Scholar 

  49. Salter DM, Wallace WH, Robb JE, et al. Human bone cell hyperpolarization response to cyclical mechanical strain is mediated by an interleukin−1beta autocrine/paracrine loop. J Bone Miner Res 2000; 15: 1746–55

    PubMed  CAS  Google Scholar 

  50. Stanford CM, Welsch F, Kastner N, et al. Primary human bone cultures from older patients do not respond at continuum levels of in vivo strain magnitudes. J Biomech 2000; 33: 63–71

    PubMed  CAS  Google Scholar 

  51. Weyts FA, Li YS, van Leeuwen J, et al. ERK activation and alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts. J Cell Biochem 2002; 87: 85–92

    PubMed  CAS  Google Scholar 

  52. Wozniak M, Fausto A, Carron CP, et al. Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3—integrin expression. J Bone Miner Res 2000; 15: 1731–45

    PubMed  CAS  Google Scholar 

  53. Yang Y, Magnay J, Cooling L, et al. Effects of substrate characteristics on bone cell response to the mechanical environment. Med Biol Eng Comput 2004; 42: 22–9

    PubMed  CAS  Google Scholar 

  54. Jansen JH, Weyts FA, Westbroek I, et al. Stretch—induced phosphorylation of ERK1/2 depends on differentiation stage of osteoblasts. J Cell Biochem 2004; 93: 542–51

    PubMed  CAS  Google Scholar 

  55. Chen YJ, Wang CJ, Yang KD, et al. Pertussis toxin—sensitive Galphai protein and ERK—dependent pathways mediate ultra—sound promotion of osteogenic transcription in human osteoblasts. FEBS Lett 2003; 554: 154–8

    PubMed  CAS  Google Scholar 

  56. Doan N, Reher P, Meghji S, et al. In vitro effects of therapeutic ultrasound on cell proliferation, protein synthesis, and cytokine production by human fibroblasts, osteoblasts, and monocytes. J Oral Maxillofac Surg 1999; 57: 409–19; discussion 420

    PubMed  CAS  Google Scholar 

  57. Harle J, Salih V, Knowles JC, et al. Effects of therapeutic ultrasound on osteoblast gene expression. J Mater Sci Mater Med 2001; 12: 1001–4

    PubMed  CAS  Google Scholar 

  58. Reher P, Harris M, Whiteman M, et al. Ultrasound stimulates nitric oxide and prostaglandin E2 production by human osteoblasts. Bone 2002; 31: 236–41

    PubMed  CAS  Google Scholar 

  59. Rosenberg N, Levy M, Francis M. Experimental model for stimulation of cultured human osteoblast—like cells by high frequency vibration. Cytotechnology 2002; 39: 125–30

    PubMed  CAS  Google Scholar 

  60. Rosenberg N. The role of the cytoskeleton in mechanotransduction in human osteoblast-like cells. Hum Exp Toxicol 2003; 22: 271–4

    PubMed  Google Scholar 

  61. Davidson RM, Tatakis DW, Auerbach AL. Multiple forms of mechanosensitive ion channels in osteoblast—like cells. Pflugers Arch 1990; 416: 646–51

    PubMed  CAS  Google Scholar 

  62. Davidson RM. Membrane stretch activates a high—conductance K+ channel in G292 osteoblastic—like cells. J Membr Biol 1993; 131: 81–92

    PubMed  CAS  Google Scholar 

  63. Hughes S, Dobson J, El Haj AJ. Mechanical stimulation of calcium signaling pathways in human bone cells using ferromagnetic micro—particles: implications for tissue engineering. Eur Cell Mater 2003; 6: 43

    Google Scholar 

  64. Jorgensen NR, Teilmann SC, Henriksen Z, et al. Activation of L—type calcium channels is required for gap junction—mediated intercellular calcium signaling in osteoblastic cells. J Biol Chem 2003; 278: 4082–6

    PubMed  CAS  Google Scholar 

  65. Pommerenke H, Schreiber E, Durr F, et al. Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. Eur J Cell Biol 1996; 70: 157–64

    PubMed  CAS  Google Scholar 

  66. Pommerenke H, Schmidt C, Durr F, et al. The mode of mechanical integrin stressing controls intracellular signaling in osteoblasts. J Bone Miner Res 2002; 17: 603–11

    PubMed  CAS  Google Scholar 

  67. Romanello M, D’Andrea P. Dual mechanism of intercellular communication in HOBIT osteoblastic cells: a role for gap—junctional hemichannels. J Bone Miner Res 2001; 16: 1465–76

    PubMed  CAS  Google Scholar 

  68. Rychly J, Pommerenke H, Durr F, et al. Analysis of spatial distributions of cellular molecules during mechanical stressing of cell surface receptors using confocal microscopy. Cell Biol Int 1998; 22: 7–12

    PubMed  CAS  Google Scholar 

  69. Schmidt C, Pommerenke H, Durr F, et al. Mechanical stressing of integrin receptors induces enhanced tyrosine phosphorylation of cytoskeletally anchored proteins. J Biol Chem 1998; 273: 5081–5

    PubMed  CAS  Google Scholar 

  70. Jorgensen NR, Teilmann SC, Henriksen Z, et al. The antiarrhythmic peptide analog rotigaptide (ZP123) stimulates gap junction intercellular communication in human osteoblasts and prevents decrease in femoral trabecular bone strength in ovariectomized rats. Endocrinology 2005; 146: 4745–54

    PubMed  Google Scholar 

  71. Walker LM, Holm A, Cooling L, et al. Mechanical manipulation of bone and cartilage cells with ‘optical tweezers’. FEBS Lett 1999; 459: 39–42

    PubMed  CAS  Google Scholar 

  72. Carmeliet G, Nys G, Stockmans I, et al. Gene expression related to the differentiation of osteoblastic cells is altered by microgravity. Bone 1998; 22: 139–43S

    Google Scholar 

  73. Gebken J, Luders B, Notbohm H, et al. Hypergravity stimulates collagen synthesis in human osteoblast—like cells: evidence for the involvement of p44/42 MAP—kinases (ERK 1/2). J Biochem (Tokyo) 1999; 126: 676–82

    CAS  Google Scholar 

  74. Kobayashi K, Kambe F, Kurokouchi K, et al. TNF—alpha—dependent activation of NF—kappa B in human osteoblastic HOS—TE85 cells is repressed in vector—averaged gravity using clinostat rotation. Biochem Biophys Res Commun 2000; 279: 258–64

    PubMed  CAS  Google Scholar 

  75. Kunisada T, Kawai A, Inoue H, et al. Effects of simulated microgravity on human osteoblast—like cells in culture. Acta Med Okayama 1997; 51: 135–40

    PubMed  CAS  Google Scholar 

  76. Brand RA, Stanford CM, Nicolella DP. Primary adult human bone cells do not respond to tissue (continuum) level strains. J Orthop Sci 2001; 6: 295–301

    PubMed  CAS  Google Scholar 

  77. Meyer CJ, Alenghat FJ, Rim P, et al. Mechanical control of cyclic AMP signalling and gene transcription through integrins. Nat Cell Biol 2000; 2: 666–8

    PubMed  CAS  Google Scholar 

  78. Grzesik WJ, Robey PG. Bone matrix RGD glycoproteins: immunolocalization and interaction with human primary osteoblastic bone cells in vitro. J Bone Miner Res 1994; 9: 487–96

    PubMed  CAS  Google Scholar 

  79. Sinha RK, Tuan RS. Regulation of human osteoblast integrin expression by orthopedic implant materials. Bone 1996; 18: 451–7

    PubMed  CAS  Google Scholar 

  80. Sawada Y, Sheetz MP. Force transduction by Triton cytoskeletons. J Cell Biol 2002; 156: 609–15

    PubMed  CAS  Google Scholar 

  81. Charras GT, Horton MA. Single cell mechanotransduction and its modulation analyzed by atomic force microscope indentation. Biophys J 2002; 82: 2970–81

    PubMed  CAS  Google Scholar 

  82. Turner CH, Takano Y, Owan I, et al. Nitric oxide inhibitor L—NAME suppresses mechanically induced bone formation in rats. Am J Physiol 1996; 270: E634–9

    Google Scholar 

  83. Lander HM, Hajjar DP, Hempstead BL, et al. A molecular redox switch on p21(ras): structural basis for the nitric oxide—p21(ras) interaction. J Biol Chem 1997; 272: 4323–6

    PubMed  CAS  Google Scholar 

  84. Gu M, Lynch J, Brecher P. Nitric oxide increases p21(Waf1/Cip1) expression by a cGMP—dependent pathway that includes activation of extracellular signal—regulated kinase and p70(S6k). J Biol Chem 2000; 275: 11389–96

    PubMed  CAS  Google Scholar 

  85. Komalavilas P, Shah PK, Jo H, et al. Activation of mitogen—activated protein kinase pathways by cyclic GMP and cyclic GMP—dependent protein kinase in contractile vascular smooth muscle cells. J Biol Chem 1999; 274: 34301–9

    PubMed  CAS  Google Scholar 

  86. Maroto R, Hamill OP. Brefeldin A block of integrin—dependent mechanosensitive ATP release from Xenopus oocytes reveals a novel mechanism of mechanotransduction. J Biol Chem 2001; 276: 23867–72

    PubMed  CAS  Google Scholar 

  87. Veitonmaki N, Cao R, Wu LH, et al. Endothelial cell surface ATP synthase—triggered caspase—apoptotic pathway is essential for k1–5−induced antiangiogenesis. Cancer Res 2004; 64: 3679–86

    PubMed  Google Scholar 

  88. Cowles EA, De Rome ME, Pastizzo G, et al. Mineralization and the expression of matrix proteins during in vivo bone development. Calcif Tissue Int 1998; 62: 74–82

    PubMed  CAS  Google Scholar 

  89. Kato M, Patel MS, Levasseur R, et al. Cbfa1−independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002; 157: 303–14

    PubMed  CAS  Google Scholar 

  90. Turner CH, Owan I, Alvey T, et al. Recruitment and proliferative responses of osteoblasts after mechanical loading in vivo determined using sustained—release bromodeoxyuridine. Bone 1998; 22: 463–9

    PubMed  CAS  Google Scholar 

  91. Bonewald LF. Osteocyte biology: its implications for osteoporosis. J Musculoskelet Neuronal Interact 2004; 4: 101–4

    PubMed  CAS  Google Scholar 

  92. Zhan M, Zhao H, Han ZC. Signalling mechanisms of anoikis. Histol Histopathol 2004; 19: 973–83

    PubMed  CAS  Google Scholar 

  93. Bucaro MA, Fertala J, Adams CS, et al. Bone cell survival in microgravity: evidence that modeled microgravity increases osteoblast sensitivity to apoptogens. Ann N Y Acad Sci 2004; 1027: 64–73

    PubMed  CAS  Google Scholar 

  94. Henriksen Z, Hiken JF, Steinberg TH, et al. The predominant mechanism of intercellular calcium wave propagation changes during long—term culture of human osteoblast—like cells. Cell Calcium 2006; 39: 435–44

    PubMed  CAS  Google Scholar 

  95. Heino TJ, Hentunen TA, Vaananen HK. Conditioned medium from osteocytes stimulates the proliferation of bone marrow mesenchymal stem cells and their differentiation into osteoblasts. Exp Cell Res 2004; 294: 458–68

    PubMed  CAS  Google Scholar 

  96. Ehrlich PJ, Lanyon LE. Mechanical strain and bone cell function: a review. Osteoporos Int 2002; 13: 688–700

    PubMed  CAS  Google Scholar 

  97. Jessop HL, Sjoberg M, Cheng MZ, et al. Mechanical strain and estrogen activate estrogen receptor alpha in bone cells. J Bone Miner Res 2001; 16: 1045–55

    PubMed  CAS  Google Scholar 

  98. Civitelli R, Ziambaras K, Warlow PM, et al. Regulation of connexin43 expression and function by prostaglandin E2 (PGE2) and parathyroid hormone (PTH) in osteoblastic cells. J Cell Biochem 1998; 68: 8–21

    PubMed  CAS  Google Scholar 

  99. Schiller PC, Mehta PP, Roos BA, et al. Hormonal regulation of intercellular communication: parathyroid hormone increases connexin 43 gene expression and gap—junctional communication in osteoblastic cells. Mol Endocrinol 1992; 6: 1433–40

    PubMed  CAS  Google Scholar 

  100. Ingber DE. Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 2003; 116: 1157–73

    PubMed  CAS  Google Scholar 

  101. Ingber DE. Tensegrity II. How structural networks influence cellular information processing networks. J Cell Sci 2003; 116: 1397–408

    PubMed  CAS  Google Scholar 

  102. van’t Hof RJ, Macphee J, Libouban H, et al. Regulation of bone mass and bone turnover by neuronal nitric oxide synthase. Endocrinology 2004; 145: 5068–74

    Google Scholar 

  103. Hart DA, Natsu-ume T, Sciore P, et al. Mechanobiology: similarities and differences between in vivo and in vitro analysis at the functional and molecular levels. Recent Res Devel Biophys Biochem 2002; 2: 153–77

    CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the support of the CIHR, the Michael Smith Foundation for Health Research, the Canadian Space Agency, and the Calgary Foundation Grace Glaum Professorship in Arthritis Research (DAH). The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexander Scott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scott, A., Khan, K.M., Duronio, V. et al. Mechanotransduction in Human Bone. Sports Med 38, 139–160 (2008). https://doi.org/10.2165/00007256-200838020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00007256-200838020-00004

Keywords

Navigation