Advertisement

Osteoblast Biology and Mechanosensing

  • Pierre J. Marie
  • Pierre J. Marie

Abstract

The skeleton adapts to unloading and loading by changes in bone formation and bone mass. Mechanical forces induce several effects on bone formation through direct and indirect effects on osteoblastogenesis. Direct effects may involve multiple mechanoreceptors expressed in osteoblasts and that are responsive to the mechanical environment. The transduction of mechanical forces to biochemical signals involves the coordination of multiple molecules and pathways including connexins, ion channels, integrins and cytoskeletal proteins, resulting in the activation of kinases and the release of signaling molecules and growth factors which control osteoblast proliferation, differentiation and survival. Notably, the Wnt signaling pathway plays a major role in controlling osteoblast fate, number and function in response to loading. The identification of the physiological mechanisms that mediate the anabolic effects of mechanical forces on osteoblastogenesis may contribute to the development of therapeutic strategies for the defective bone formation in disuse osteoporosis.

Keywords

Bone Formation Focal Adhesion Kinase Mechanical Force Osteoblast Differentiation Osteoblastic Cell 
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.

Notes

Acknowledgments

Due to space limitations, only a selected number of references on the subject could be quoted in this chapter. The reader is invited to read the indicated reviews for a larger selection of papers related to the subject. The author’s work on skeletal unloading was in part supported by the French National Spatial Agency (CNES, Paris, France).

References

  1. Aguirre JI, Plotkin LI, Stewart SA, Weinstein RS, Parfitt AM, Manolagas SC, Bellido T (2006) Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res 21(4)  :  605–615PubMedCrossRefGoogle Scholar
  2. Aguirre JI, Plotkin LI, Gortazar AR, Millan MM, O’Brien CA, Manolagas SC, Bellido T (2007) A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J Biol Chem 282(35)  :  25501–25508PubMedCrossRefGoogle Scholar
  3. Ahdjoudj S, Lasmoles F, Holy X, Zérath E, Marie PJ (2002) Transforming growth factor inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma. J Bone Miner Res 17(4)  :  668–677PubMedCrossRefGoogle Scholar
  4. Ahdjoudj S, Fromigué O, Marie PJ (2004) Plasticity and regulation of human bone marrow stromal cells:potential implication in the treatment of age-related bone loss. Histol Histopathol 19  :  151–157PubMedGoogle Scholar
  5. Ahdjoudj S, Kaabeche K, Holy X, Fromigué O, Modrowski D, Zérath E, Marie PJ (2005) Transforming growth factor-beta inhibits CCAAT/enhancer-binding protein expression and PPARgamma activity in unloaded bone marrow stromal cells. Exp Cell Res 303(1)  :  138–147PubMedCrossRefGoogle Scholar
  6. Ajubi NE, Klein-Nulend J, Alblas MJ, Burger EH, Nijweide PJ (1999) Signal transduction pathways involved in fluid flow-induced PGE2 production by cultured osteocytes. Am J Physiol 276(1 Pt 1)  :  E171–E178PubMedGoogle Scholar
  7. Armstrong VJ, Muzylak M, Sunters A, Zaman G, Saxon LK, Price JS, Lanyon LE (2007) Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J Biol Chem 282(28)  :  20715–20727PubMedCrossRefGoogle Scholar
  8. Arnsdorf EJ, Tummala P, Jacobs CR (2009) Non-canonical Wnt signaling and N-cadherin related beta-catenin signaling play a role in mechanically induced osteogenic cell fate. PLoS One 4(4)  :  e5388PubMedCrossRefGoogle Scholar
  9. Aubin JE (2001) Regulation of osteoblast formation and function. Rev Endocr Metab Disord 2(1)  :  81–94PubMedCrossRefGoogle Scholar
  10. Bancroft GN, Sikavitsas VI, van den Dolder J, Sheffield TL, Ambrose CG, Jansen JA, Mikos AG (2002) Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc Natl Acad Sci USA 99(20)  :  12600–12605PubMedCrossRefGoogle Scholar
  11. Barou O, Palle S, Vico L, Alexandre C, Lafage-Proust MH (1998) Hindlimb unloading in rat decreases preosteoblast proliferation assessed in vivo with BrdU incorporation. Am J Physiol 274(1 Pt 1)  :  E108–E114PubMedGoogle Scholar
  12. Basso N, Heersche JN (2002) Characteristics of in vitro osteoblastic cell loading models. Bone 30(2)  :  347–351PubMedCrossRefGoogle Scholar
  13. Bateman TA, Dunstan CR, Ferguson VL, Lacey DL, Ayers RA, Simske SJ (2000) Osteoprotegerin mitigates tail suspension-induced osteopenia. Bone 26(5)  :  443–449PubMedCrossRefGoogle Scholar
  14. Bikle DD (2008) Integrins, insulin like growth factors, and the skeletal response to load. Osteoporos Int 19(9)  :  1237–1246PubMedCrossRefGoogle Scholar
  15. Bikle DD, Halloran BP (1999) The response of bone to unloading. J Bone Miner Metab 17(4)  :  233–244PubMedCrossRefGoogle Scholar
  16. Bikle DD, Harris J, Halloran BP, Morey-Holton E (1994) Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation. Am J Physiol 267(6 Pt 1)  :  E822–E827PubMedGoogle Scholar
  17. Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42(4)  :  606–615PubMedCrossRefGoogle Scholar
  18. Boppart MD, Kimmel DB, Yee JA, Cullen DM (1998) Time course of osteoblast appearance after in vivo mechanical loading. Bone 5  :  409–415CrossRefGoogle Scholar
  19. Boutahar N, Guignandon A, Vico L, Lafage-Proust MH (2004) Mechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 tyrosine sites involved in ERK activation. J Biol Chem 279(29)  :  30588–30599PubMedCrossRefGoogle Scholar
  20. Burger EH, Klein-Nulend J (1998) Microgravity and bone cell mechanosensitivity. Bone 22(5 Suppl)  :  127S–130SPubMedCrossRefGoogle Scholar
  21. Burr DB, Robling AG, Turner CH (2002) Effects of biomechanical stress on bones in animals. Bone 30(5)  :  781–786PubMedCrossRefGoogle Scholar
  22. Capulli M, Rufo A, Teti A, Rucci N (2009) Global transcriptome analysis in mouse calvarial osteoblasts highlights sets of genes regulated by modeled microgravity and identifies a “mechanoresponsive osteoblast gene signature”. J Cell Biochem 107(2)  :  240–252PubMedCrossRefGoogle Scholar
  23. Carvalho RS, Scott JE, Suga DM, Yen EH (1994) Stimulation of signal transduction pathways in osteoblasts by mechanical strain potentiated by parathyroid hormone. J Bone Miner Res 9(7)  :  999–1011PubMedCrossRefGoogle Scholar
  24. Carvalho RS, Schaffer JL, Gerstenfeld LC (1998) Osteoblasts induce osteopontin expression in response to attachment on fibronectin: demonstration of a common role for integrin receptors in the signal transduction processes of cell attachment and mechanical stimulation. J Cell Biochem 70(3)  :  376–390PubMedCrossRefGoogle Scholar
  25. Carvalho RS, Bumann A, Schaffer JL, Gerstenfeld LC (2002) Predominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation. J Cell Biochem 84(3)  :  497–508PubMedCrossRefGoogle Scholar
  26. Case N, Ma M, Sen B, Xie Z, Gross TS, Rubin J (2008) Beta-catenin levels influence rapid mechanical responses in osteoblasts. J Biol Chem 283(43)  :  29196–29205PubMedCrossRefGoogle Scholar
  27. Chen KD, Li YS, Kim M, Li S, Yuan S, Chien S, Shyy JY (1999) Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J Biol Chem 274(26)  :  18393–18400PubMedCrossRefGoogle Scholar
  28. Chen NX, Geist DJ, Genetos DC, Pavalko FM, Duncan RL (2003) Fluid shear-induced NFkappaB translocation in osteoblasts is mediated by intracellular calcium release. Bone 33(3)  :  399–410PubMedCrossRefGoogle Scholar
  29. Cheng MZ, Rawlinson SC, Pitsillides AA, Zaman G, Mohan S, Baylink DJ, Lanyon LE (2002) 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 17(4)  :  593–602PubMedCrossRefGoogle Scholar
  30. Cherian PP, Siller-Jackson AJ, Gu S, Wang X, Bonewald LF, Sprague E, Jiang JX (2005) Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Mol Biol Cell 16(7)  :  3100–3106PubMedCrossRefGoogle Scholar
  31. Cowin SC (1998) On mechanosensation in bone under microgravity. Bone 22  :  119S–125SPubMedCrossRefGoogle Scholar
  32. David V, Lafage-Proust MH, Laroche N, Christian A, Ruegsegger P, Vico L (2006) Two-week longitudinal survey of bone architecture alteration in the hindlimb-unloaded rat model of bone loss: sex differences. Am J Physiol Endocrinol Metab 290(3)  :  E440–E447PubMedCrossRefGoogle Scholar
  33. David V, Martin A, Lafage-Proust MH, Malaval L, Peyroche S, Jones DB, Vico L, Guignandon A (2007) Mechanical loading down-regulates peroxisome proliferator-activated receptor gamma in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis. Endocrinology 148(5):2553–2562PubMedCrossRefGoogle Scholar
  34. Davidson RM, Tatakis DW, Auerbach AL (1990) Multiple forms of mechanosensitive ion channels in osteoblast-like cells. Pflugers Arch 416(6)  :  646–651PubMedCrossRefGoogle Scholar
  35. Donahue HJ (2000) Gap junctions and biophysical regulation of bone cell differentiation. Bone 26(5)  :  417–422PubMedCrossRefGoogle Scholar
  36. Drissi H, Lomri A, Lasmoles F, Holy X, Zerath E, Marie PJ (1999) Skeletal unloading induces biphasic changes in insulin like growth factor-I mRNA levels and osteoblast activity. Exp Cell Res 251  :  275–284PubMedCrossRefGoogle Scholar
  37. Dufour C, Holy X, Marie PJ (2007) Skeletal unloading induces osteoblast apoptosis and targets alpha5beta1-PI3K-Bcl-2 signaling in rat bone. Exp Cell Res 313(2)  :  394–403PubMedCrossRefGoogle Scholar
  38. Dufour C, Holy X, Marie PJ (2008) Transforming growth factor-beta prevents osteoblast apoptosis induced by skeletal unloading via PI3K/Akt, Bcl-2, and phospho-Bad signaling. Am J Physiol Endocrinol Metab 294(4)  :  E794–E801PubMedCrossRefGoogle Scholar
  39. Duncan RL, Turner CH (1995) Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int 57  :  344–358PubMedCrossRefGoogle Scholar
  40. El Haj AJ, Minter SL, Rawlinson SCF, Suswillo R, Lanyon LE (1990) Cellular responses to mechanical loading in vitro. J Bone Miner Res 5  :  923–932PubMedCrossRefGoogle Scholar
  41. Fan X, Roy E, Zhu L, Murphy TC, Ackert-Bicknell C, Hart CM, Rosen C, Nanes MS, Rubin J (2004) Nitric oxide regulates receptor activator of nuclear factor-kappaB ligand and osteoprotegerin expression in bone marrow stromal cells. Endocrinology 145(2)  :  751–759PubMedCrossRefGoogle Scholar
  42. Forwood MR, Turner CH (1995) Skeletal adaptations to mechanical usage: results from tibial loading studies in rats. Bone 17(4 Suppl)  :  197S–205SGoogle Scholar
  43. Faure C, Linossier MT, Malaval L, Lafage-Proust MH, Peyroche S, Vico L, Guignandon A (2008) Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation. Bone 42(6)  :  1092–1101PubMedCrossRefGoogle Scholar
  44. Frost HM (2003) Bone’s mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol 275(2)  :  1081–1101PubMedCrossRefGoogle Scholar
  45. Genetos DC, Geist DJ, Liu D, Donahue HJ, Duncan RL (2005) Fluid shear-induced ATP secretion mediates prostaglandin release in MC3T3-E1 osteoblasts. J Bone Miner Res 20(1)  :  41–49PubMedCrossRefGoogle Scholar
  46. Geng WD, Boskovic G, Fultz ME, Li C, Niles RM, Ohno S, Wright GL (2001) Regulation of expression and activity of four PKC isozymes in confluent and mechanically stimulated UMR-108 osteoblastic cells. J Cell Physiol 189(2)  :  216–228PubMedCrossRefGoogle Scholar
  47. Globus RK, Bikle DD, Morey-Holton E (1986) The temporal response of bone to unloading. Endocrinology 118(2)  :  733–742PubMedCrossRefGoogle Scholar
  48. Granet C, Boutahar N, Vico L, Alexandre C, Lafage-Proust MH (2001) MAPK and SRC-kinases control EGR-1 and NF-kappa B inductions by changes in mechanical environment in osteoblasts. Biochem Biophys Res Commun 284(3)  :  622–631PubMedCrossRefGoogle Scholar
  49. Granet C, Vico AG, Alexandre C, Lafage-Proust MH (2002) MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells. Cell Signal 14(8)  :  679–688PubMedCrossRefGoogle Scholar
  50. Grano M, Mori G, Minielli V, Barou O, Colucci S, Giannelli G, Alexandre C, Zallone AZ, Vico L (2002) Rat hindlimb unloading by tail suspension reduces osteoblast differentiation, induces IL-6 secretion, and increases bone resorption in ex vivo cultures. Calcif Tissue Int 70(3)  :  176–185PubMedCrossRefGoogle Scholar
  51. Grimston SK, Screen J, Haskell JH, Chung DJ, Brodt MD, Silva MJ, Civitelli R (2006) Role of connexin43 in osteoblast response to physical load. Ann N Y Acad Sci 1068  :  214–224PubMedCrossRefGoogle Scholar
  52. Grimston SK, Brodt MD, Silva MJ, Civitelli R (2008) Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the connexin43 gene (Gja1). J Bone Miner Res 23(6)  :  879–886PubMedCrossRefGoogle Scholar
  53. Guignandon A, Usson Y, Laroche N, Lafage-Proust MH, Sabido O, Alexandre C, Vico L (1997) Effects of intermittent or continuous gravitational stresses on cell- matrix adhesion: quantitative analysis of focal contacts in osteoblastic ROS 17/2.8 cells. Exp Cell Res 236  :  66–75PubMedCrossRefGoogle Scholar
  54. Harter LV, Hruska KA, Duncan RL (1995) Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. Endocrinology 136(2)  :  528–535PubMedCrossRefGoogle Scholar
  55. Hens JR, Wilson KM, Dann P, Chen X, Horowitz MC, Wysolmerski JJ (2005) TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro. J Bone Miner Res 20(7)  :  1103–1113PubMedCrossRefGoogle Scholar
  56. Hillam RA, Skerry TM (1995) Inhibition of bone resorption and stimulation of formation by mechanical loading of the modeling rat ulna in vivo. J Bone Miner Res 10(5)  :  683–689PubMedCrossRefGoogle Scholar
  57. Hino K, Nakamoto T, Nifuji A, Morinobu M, Yamamoto H, Ezura Y, Noda M (2007) Deficiency of CIZ, a nucleocytoplasmic shuttling protein, prevents unloading-induced bone loss through the enhancement of osteoblastic bone formation in vivo. Bone 40(4)  :  852–860PubMedCrossRefGoogle Scholar
  58. Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD (2000) Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature 405(6787)  :  704–706PubMedCrossRefGoogle Scholar
  59. Inoue D, Kido S, Matsumoto T (2004) Transcriptional induction of FosB/DeltaFosB gene by mechanical stress in osteoblasts. J Biol Chem 279(48)  :  49795–49803PubMedCrossRefGoogle Scholar
  60. 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(3)  :  399–404PubMedCrossRefGoogle Scholar
  61. Jackson WM, Jaasma MJ, Tang RY, Keaveny TM (2008) Mechanical loading by fluid shear is sufficient to alter the cytoskeletal composition of osteoblastic cells. Am J Physiol Cell Physiol 295(4)  :  C1007–C1015PubMedCrossRefGoogle Scholar
  62. Jagger CJ, Chow JW, Chambers TJ (1996) Estrogen suppresses activation but enhances formation phase of osteogenic response to mechanical stimulation in rat bone. J Clin Invest 98(10)  :  2351–2357PubMedCrossRefGoogle Scholar
  63. Jalali S, del Pozo MA, Chen K, Miao H, Li Y, Schwartz MA, Shyy JY, Chien S (2001) Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc Natl Acad Sci USA 98(3)  :  1042–1046PubMedCrossRefGoogle Scholar
  64. Jessop HL, Sjoberg M, Cheng MZ, Zaman G, Wheeler-Jones CP, Lanyon LE (2001) Mechanical strain and estrogen activate estrogen receptor alpha in bone cells. J Bone Miner Res 16(6)  :  1045–1055PubMedCrossRefGoogle Scholar
  65. Jones D, Leivseth G, Tenbosch J (1995) Mechano-reception in osteoblast-like cells. Biochem Cell Biol 73  :  525–534PubMedCrossRefGoogle Scholar
  66. Kanematsu M, Yoshimura K, Takaoki M, Sato A (2002) Vector-averaged gravity regulates gene expression of receptor activator of NF-kappaB (RANK) ligand and osteoprotegerin in bone marrow stromal cells via cyclic AMP/protein kinase A pathway. Bone 30(4)  :  553–558PubMedCrossRefGoogle Scholar
  67. Kapur S, Baylink DJ, Lau KH (2003) Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 3  :  241–251CrossRefGoogle Scholar
  68. Kaspar D, Seidl W, Neidlinger-Wilke C, Beck A, Claes L, Ignatius A (2002) Proliferation of human-derived osteoblast-like cells depends on the cycle number and frequency of uniaxial strain. J Biomech 35(7)  :  873–880PubMedCrossRefGoogle Scholar
  69. Katsumi A, Orr AW, Tzima E, Schwartz MA (2004) Integrins in mechanotransduction. J Biol Chem 279(13)  :  12001–12004PubMedCrossRefGoogle Scholar
  70. Kawamura S, Miyamoto S, Brown JH (2003) Initiation and transduction of stretch-induced RhoA and Rac1 activation through caveolae: cytoskeletal regulation of ERK translocation. J Biol Chem 278(33)  :  31111–31117PubMedCrossRefGoogle Scholar
  71. Keila S, Pitaru S, Grosskopf A, Weinreb M (1994) Bone marrow from mechanically unloaded rat bones expresses reduced osteogenic capacity in vitro. J Bone Miner Res 9(3)  :  321–327PubMedCrossRefGoogle Scholar
  72. Khatiwala CB, Kim PD, Peyton SR, Putnam AJ (2009) ECM compliance regulates osteogenesis by influencing MAPK signaling downstream of RhoA and ROCK. J Bone Miner Res 24(5)  :  886–898PubMedCrossRefGoogle Scholar
  73. Klein-Nulend J, Roelofsen J, Sterck JG, Semeins CM, Burger EH (1995) Mechanical loading stimulates the release of transforming growth factor- beta activity by cultured mouse calvariae and periosteal cells. J Cell Physiol 163  :  115–119PubMedCrossRefGoogle Scholar
  74. Klein-Nulend J, Burger EH, Semeins CM, Raisz LG, Pilbeam CC (1997) Pulsating fluid flow stimulates prostaglandin release and inducible prostaglandin G/H synthase mRNA expression in primary mouse bone cells. J Bone Miner Res 12  :  45–51PubMedCrossRefGoogle Scholar
  75. Kletsas D, Basdra EK, Papavassiliou AG (2002) Effect of protein kinase inhibitors on the stretch-elicited c-Fos and c-Jun up-regulation in human PDL osteoblast-like cells. J Cell Physiol 190(3)  :  313–321PubMedCrossRefGoogle Scholar
  76. Kostenuik PJ, Halloran BP, Morey-Holton ER, Bikle DD (1997) Skeletal unloading inhibits the in vitro proliferation and differentiation of rat osteoprogenitor cells. Am J Physiol 273(6 Pt 1)  :  E1133–E1139PubMedGoogle Scholar
  77. Lau KH, Kapur S, Kesavan C, Baylink DJ (2006) Up-regulation of the Wnt, estrogen receptor, insulin-like growth factor-I, and bone morphogenetic protein pathways in C57BL/6J osteoblasts as opposed to C3H/HeJ osteoblasts in part contributes to the differential anabolic response to fluid shear. J Biol Chem 281(14)  :  9576–9588PubMedCrossRefGoogle Scholar
  78. Li Z, Zhou Z, Yellowley CE, Donahue HJ (1999) Inhibiting gap junctional intercellular communication alters expression of differentiation markers in osteoblastic cells. Bone 25(6)  :  661–666Google Scholar
  79. Li J, Chen G, Zheng L, Luo S, Zhao Z (2007) Osteoblast cytoskeletal modulation in response to compressive stress at physiological levels. Mol Cell Biochem 304(1–2)  :  45–52PubMedCrossRefGoogle Scholar
  80. Machwate M, Zerath E, Holy X, Hott H, Modrowski D, Malouvier A, Marie PJ (1993) Skeletal unloading in rat decreases proliferation of rat bone and marrow-derived osteoblastic cells. Am J Physiol Endocrinol Metab 27  :  E790–E799Google Scholar
  81. Machwate M, Zerath E, Holy X, Hott M, Pastoureau P, Marie PJ (1994) Insulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats. Endocrinology 134(3)  :  1031–1038PubMedCrossRefGoogle Scholar
  82. Machwate M, Zerath E, Holy X, Hott M, GodetD LA, Marie PJ (1995) Systemic administration of transforming growth factor-β 2 prevents the impaired bone formation and osteopenia induced by unloading in rats. J Clin Invest 96  :  1245–1253PubMedCrossRefGoogle Scholar
  83. Malone AM, Batra NN, Shivaram G, Kwon RY, You L, Kim CH, Rodriguez J, Jair K, Jacobs CR (2007a) The role of actin cytoskeleton in oscillatory fluid flow-induced signaling in MC3T3-E1 osteoblasts. Am J Physiol Cell Physiol 292(5)  :  C1830–1836PubMedCrossRefGoogle Scholar
  84. Malone AM, Anderson CT, Tummala P, Kwon RY, Johnston TR, Stearns T, Jacobs CR (2007b) Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc Natl Acad Sci USA 104(33)  :  13325–13330PubMedCrossRefGoogle Scholar
  85. Marie PJ (2008) Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys 473(2)  :  98–105PubMedCrossRefGoogle Scholar
  86. Marie PJ, Kaabeche K (2006) PPAR gamma activity and control of bone mass in skeletal unloading. PPAR Res 2006  :  64807PubMedCrossRefGoogle Scholar
  87. Marie PJ, Zerath E (2000) Role of growth factors in osteoblast alterations induced by skeletal unloading in rats. Growth Factors 18(1)  :  1–10PubMedCrossRefGoogle Scholar
  88. Marie PJ, Jones D, Vico L, Zallone A, Hinsenkamp M, Cancedda R (2000) Osteobiology, strain and microgravity. Part I: Studies at the cellular level. Calcif Tissue Int 67(1)  :  2–9PubMedCrossRefGoogle Scholar
  89. Mason DJ (2004) Glutamate signalling and its potential application to tissue engineering of bone. Eur Cell Mater 7  :  12–25PubMedGoogle Scholar
  90. McAllister TN, Frangos JA (1999) Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways. J Bone Miner Res 14(6)  :  930–936PubMedCrossRefGoogle Scholar
  91. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6(4)  :  483–495PubMedCrossRefGoogle Scholar
  92. Meyers VE, Zayzafoon M, Gonda SR, Gathings WE, McDonald JM (2004) Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells. J Cell Biochem 93(4)  :  697–707PubMedCrossRefGoogle Scholar
  93. Meyers VE, Zayzafoon M, Douglas JT, McDonald JM (2005) RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res 20(10)  :  1858–1866PubMedCrossRefGoogle Scholar
  94. Miles RR, Turner CH, Santerre R, Tu Y, McClelland P, Argot J, DeHoff BS, Mundy CW, Rosteck PR Jr, Bidwell J, Sluka JP, Hock J, Onyia JE (1998) Analysis of differential gene expression in rat tibia after an osteogenic stimulus in vivo: mechanical loading regulates osteopontin and myeloperoxidase. J Cell Biochem 68(3)  :  355–365PubMedCrossRefGoogle Scholar
  95. Morey-Holton ER, Globus RK (1998) Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight. Bone 22(5 Suppl)  :  83S–88SPubMedCrossRefGoogle Scholar
  96. Motokawa M, Kaku M, Tohma Y, Kawata T, Fujita T, Kohno S, Tsutsui K, Ohtani J, Tenjo K, Shigekawa M, Kamada H, Tanne K (2005) Effects of cyclic tensile forces on the expression of vascular endothelial growth factor (VEGF) and macrophage-colony-stimulating factor (M-CSF) in murine osteoblastic MC3T3-E1 cells. J Dent Res 84(5)  :  422–427PubMedCrossRefGoogle Scholar
  97. Mullender MG, Dijcks SJ, Bacabac RG, Semeins CM, Van Loon JJ, Klein-Nulend J (2006) Release of nitric oxide, but not prostaglandin E2, by bone cells depends on fluid flow frequency. J Orthop Res 24(6)  :  1170–1177PubMedCrossRefGoogle Scholar
  98. Nomura S, Takano-Yamamoto T (2000) Molecular events caused by mechanical stress in bone. Matrix Biol 19(2)  :  91–96PubMedCrossRefGoogle Scholar
  99. Norvell SM, Ponik SM, Bowen DK, Gerard R, Pavalko FM (2004) Fluid shear stress induction of COX-2 protein and prostaglandin release in cultured MC3T3-E1 osteoblasts does not require intact microfilaments or microtubules. J Appl Physiol 96(3)  :  957–966PubMedCrossRefGoogle Scholar
  100. Owan I, Burr DB, Turner CH, Qiu J, Tu Y, Onyia JE, Duncan RL (1997) Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain. Am J Physiol 273(3 Pt 1)  :  C810–C815PubMedGoogle Scholar
  101. Ozawa H, Imamura K, Abe E, Takahashi N, Hiraide T, Shibasaki Y, Fukuhara T, Suda T (1990) Effect of a continuously applied compressive pressure on mouse osteoblast-like cells (MC3T3-E1) in vitro. J Cell Physiol 142(1)  :  177–185PubMedCrossRefGoogle Scholar
  102. Pavalko FM, Chen NX, Turner CH, Burr DB, Atkinson S, Hsieh YF, Qiu J, Duncan RL (1998) Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. Am J Physiol 275(6 Pt 1)  :  C1591–C1601PubMedGoogle Scholar
  103. Pavalko FM, Norvell SM, Burr DB, Turner CH, Duncan RL, Bidwell JP (2003a) A model for mechanotransduction in bone cells: the load-bearing mechanosomes. J Cell Biochem 88(1)  :  104–112PubMedCrossRefGoogle Scholar
  104. Pavalko FM, Gerard RL, Ponik SM, Gallagher PJ, Jin Y, Norvell SM (2003b) Fluid shear stress inhibits TNF-alpha-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3. J Cell Physiol 194(2)  :  194–205PubMedCrossRefGoogle Scholar
  105. Pavlin D, Zadro R, Gluhak-Heinrich J (2001) Temporal pattern of stimulation of osteoblast-associated genes during mechanically-induced osteogenesis in vivo: early responses of osteocalcin and type I collagen. Connect Tissue Res 42(2)  :  135–148PubMedCrossRefGoogle Scholar
  106. Peake MA, Cooling LM, Magnay JL, Thomas PB, El Haj AJ (2000) Selected contribution: regulatory pathways involved in mechanical induction of c-fos gene expression in bone cells. J Appl Physiol 89(6)  :  2498–2507PubMedGoogle Scholar
  107. Pommerenke H, Schmidt C, Durr F, Nebe B, Luthen F, Muller P, Rychly J (2002) The mode of mechanical integrin stressing controls intracellular signaling in osteoblasts. J Bone Miner Res 17(4)  :  603–611PubMedCrossRefGoogle Scholar
  108. Rath B, Nam J, Knobloch TJ, Lannutti JJ, Agarwal S (2008) Compressive forces induce osteogenic gene expression in calvarial osteoblasts. J Biomech 41(5)  :  1095–1103PubMedCrossRefGoogle Scholar
  109. Rawlinson SC, el-Haj AJ, Minter SL, Tavares IA, Bennett A, Lanyon LE (1991) Loading-related increases in prostaglandin production in cores of adult canine cancellous bone in vitro: a role for prostacyclin in adaptive bone remodeling? J Bone Miner Res 6(12)  :  1345–1351Google Scholar
  110. Rawlinson SC, Mohan S, Baylink DJ, Lanyon LE (1993) Exogenous prostacyclin, but not prostaglandin E2, produces similar responses in both G6PD activity and RNA production as mechanical loading, and increases IGF-II release, in adult cancellous bone in culture. Calcif Tissue Int 53(5)  :  324–329PubMedCrossRefGoogle Scholar
  111. Rawlinson SC, Mosley JR, Suswillo RF, Pitsillides AA, Lanyon LE (1995) Calvarial and limb bone cells in organ and monolayer culture do not show the same early responses to dynamic mechanical strain. J Bone Miner Res 10(8)  :  1225–1232PubMedCrossRefGoogle Scholar
  112. Rawlinson SC, Pitsillides AA, Lanyon LE (1996) Involvement of different ion channels in osteoblasts’ and osteocytes’ early responses to mechanical strain. Bone 19(6)  :  609–614PubMedCrossRefGoogle Scholar
  113. Reich KM, Frangos JA (1991) Effect of flow on prostaglandin E2 and inositol trisphosphate levels in osteoblasts. Am J Physiol 261(3 Pt 1)  :  C428–C432PubMedGoogle Scholar
  114. Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, Cullen DM, Zhao W, Li C, Kharode Y, Sauter L, Babij P, Brown EL, Hill AA, Akhter MP, Johnson ML, Recker RR, Komm BS, Bex FJ (2006) Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem 281(42)  :  31720–31728PubMedCrossRefGoogle Scholar
  115. Robling AG, Castillo AB, Turner CH (2006) Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8  :  455–498PubMedCrossRefGoogle Scholar
  116. Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283(9)  :  5866–5875PubMedCrossRefGoogle Scholar
  117. Rubin J, Murphy T, Nanes MS, Fan X (2000) Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells. Am J Physiol Cell Physiol 278(6)  :  C1126–C1132PubMedGoogle Scholar
  118. Rubin C, Turner AS, Bain S, Mallinckrodt C, Anabolism McLeod K (2001) Low mechanical signals strengthen long bones. Nature 412(6847)  :  603–604PubMedCrossRefGoogle Scholar
  119. Rubin J, Murphy TC, Fan X, Goldschmidt M, Taylor WR (2002) Activation of extracellular signal-regulated kinase is involved in mechanical strain inhibition of RANKL expression in bone stromal cells. J Bone Miner Res 17(8)  :  1452–1460PubMedCrossRefGoogle Scholar
  120. Rubin J, Rubin C, Jacobs CR (2006) Molecular pathways mediating mechanical signaling in bone. Gene 367  :  1–16PubMedCrossRefGoogle Scholar
  121. Rucci N, Rufo A, Alamanou M, Teti A (2007) Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio. J Cell Biochem 100(2)  :  464–473PubMedCrossRefGoogle Scholar
  122. Ryder KD, Duncan RL (2000) Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation. Calcif Tissue Int 67(3)  :  241–246PubMedCrossRefGoogle Scholar
  123. 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(1)  :  119–127PubMedCrossRefGoogle Scholar
  124. 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(5)  :  2296–2305PubMedCrossRefGoogle Scholar
  125. Salter DM, Robb JE, Wright MO (1997) Electrophysiological responses of human bone cells to mechanical stimulation: evidence for specific integrin function in mechanotransduction. Bone Miner Res 12(7)  :  1133–1141CrossRefGoogle Scholar
  126. Saunders MM, Taylor AF, Du C, Zhou Z, Pellegrini VD Jr, Donahue HJ (2006) Mechanical stimulation effects on functional end effectors in osteoblastic MG-63 cells. J Biomech 39(8)  :  1419–1427PubMedCrossRefGoogle Scholar
  127. Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH (2006) The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem 281(33)  :  23698–23711PubMedCrossRefGoogle Scholar
  128. Sen B, Xie Z, Case N, Ma M, Rubin C, Rubin J (2008) Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology 149(12)  :  6065–6075PubMedCrossRefGoogle Scholar
  129. Shyy JY, Chien S (1997) Role of integrins in cellular responses to mechanical stress and adhesion. Curr Opin Cell Biol 9(5)  :  707–713PubMedCrossRefGoogle Scholar
  130. Sikavitsas VI, Bancroft GN, Holtorf HL, Jansen JA, Mikos AG (2003) Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces. Proc Natl Acad Sci USA 100(25)  :  14683–14688PubMedCrossRefGoogle Scholar
  131. Skerry TM (2008) The response of bone to mechanical loading and disuse: fundamental principles and influences on osteoblast/osteocyte homeostasis. Arch Biochem Biophys 473(2)  :  117–123PubMedCrossRefGoogle Scholar
  132. Skerry TM, Genever PG (2001) Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci 22(4)  :  174–181PubMedCrossRefGoogle Scholar
  133. Smalt R, Mitchell FT, Howard RL, Chambers TJ (1997) Induction of NO and prostaglandin E2 in osteoblasts by wall-shear stress but not mechanical strain. Am J Physiol 273(4 Pt 1)  :  E751–E758PubMedGoogle Scholar
  134. Szczesniak AM, Gilbert RW, Mukhida M, Anderson GI (2005) Mechanical loading modulates glutamate receptor subunit expression in bone. Bone 37(1)  :  63–73PubMedCrossRefGoogle Scholar
  135. Tanabe Y, Koga M, Saito M, Matsunaga Y, Nakayama K (2004) Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPARgamma2. J Cell Sci 117(Pt 16)  :  3605–3614PubMedCrossRefGoogle Scholar
  136. Terai K, Takano-Yamamoto T, Ohba Y, Hiura K, Sugimoto M, Sato M, Kawahata H, Inaguma N, Kitamura Y, Nomura S (1999) Role of osteopontin in bone remodeling caused by mechanical stress. J Bone Miner Res 14(6)  :  839–849PubMedCrossRefGoogle Scholar
  137. Toma CD, Ashkar S, Gray ML, Schaffer JL, Gerstenfeld LC (1997) Signal transduction of mechanical stimuli is dependent on microfilament integrity: identification of osteopontin as a mechanically induced gene in osteoblasts. J Bone Miner Res 12  :  1626–1636PubMedCrossRefGoogle Scholar
  138. Turner CH (1992) Functional determinants of bone structure: beyond Wolff’s law of bone transformation. Bone 13(6)  :  403–409PubMedCrossRefGoogle Scholar
  139. Turner CH (1998) Three rules for bone adaptation to mechanical stimuli. Bone 23(5)  :  399–407Google Scholar
  140. Turner CH, Owan I, Alvey T, Hulman J, Hock JM (1998) Recruitment and proliferative responses of osteoblasts after mechanical loading in vivo determined using sustained-release bromodeoxyuridine. Bone 22(5)  :  463–469PubMedCrossRefGoogle Scholar
  141. Turner CH, Warden SJ, Bellido T, Plotkin LI, Kumar N, Jasiuk I, Danzig J, Robling AG (2009) Mechanobiology of the skeleton. Sci Signal 2(68)  :  pt3PubMedCrossRefGoogle Scholar
  142. Vico L, Hinsenkamp M, Jones D, Marie PJ, Zallone A, Cancedda R (2001) Osteobiology, strain and microgravity. Part II: Studies at the tissue level. Calcif Tissue Int 68(1)  :  1–10PubMedCrossRefGoogle Scholar
  143. Wadhwa S, Godwin SL, Peterson DR, Epstein MA, Raisz LG, Pilbeam CC (2002) Fluid flow induction of cyclo-oxygenase 2 gene expression in osteoblasts is dependent on an extracellular signal-regulated kinase signaling pathway. J Bone Miner Res 17(2)  :  266–274PubMedCrossRefGoogle Scholar
  144. Wakley GK, Portwood JS, Turner RT (1992) Disuse osteopenia is accompanied by downregulation of gene expression for bone proteins in growing rats. Am J Physiol 263(6 Pt 1)  :  E1029–E1034PubMedGoogle Scholar
  145. Weyts FA, Li YS, van Leeuwen J, Weinans H, Chien S (2002) ERK activation and alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts. J Cell Biochem 87(1)  :  85–92PubMedCrossRefGoogle Scholar
  146. Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer BS, Guo D, Dallas SL, Maser R, Calvet JP, Bonewald L, Quarles LD (2006) Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem 281(41)  :  30884–30895PubMedCrossRefGoogle Scholar
  147. Yamaguchi M, Kishi S (1994) Differential effects of insulin and insulin-like growth factor-I in the femoral tissues of rats with skeletal unloading. Calcif Tissue Int 55(5)  :  363–367PubMedCrossRefGoogle Scholar
  148. Yao Z, Lafage-Proust MH, Plouët J, Bloomfield S, Alexandre C, Vico L (2004) Increase of both angiogenesis and bone mass in response to exercise depends on VEGF. J Bone Miner Res 19(9)  :  1471–1480PubMedCrossRefGoogle Scholar
  149. Yeh CK, Rodan GA (1984) Tensile forces enhance prostaglandin E synthesis in osteoblastic cells grown on collagen ribbons. Calcif Tissue Int 36(Suppl 1)  :  S67–S71PubMedCrossRefGoogle Scholar
  150. Yellowley CE, Li Z, Zhou Z, Jacobs CR, Donahue HJ (2000) Functional gap junctions between osteocytic and osteoblastic cells. J Bone Miner Res 15(2)  :  209–217PubMedCrossRefGoogle Scholar
  151. You J, Reilly GC, Zhen X, Yellowley CE, Chen Q, Donahue HJ, Jacobs CR (2001) Osteopontin gene regulation by oscillatory fluid flow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in MC3T3-E1 osteoblasts. J Biol Chem 276(16)  :  13365–13371PubMedCrossRefGoogle Scholar
  152. Zaman G, Suswillo RF, Cheng MZ, Tavares IA, Lanyon LE (1997) Early responses to dynamic strain change and prostaglandins in bone-derived cells in culture. J Bone Miner Res 12(5)  :  769–777Google Scholar
  153. Zaman G, Pitsillides AA, Rawlinson SC, Suswillo RF, Mosley JR, Cheng MZ, Platts LA, Hukkanen M, Polak JM, Lanyon LE (1999) Mechanical strain stimulates nitric oxide production by rapid activation of endothelial nitric oxide synthase in osteocytes. J Bone Miner Res 14(7)  :1123–1131Google Scholar
  154. Zaman G, Cheng MZ, Jessop HL, White R, Lanyon LE (2000) Mechanical strain activates estrogen response elements in bone cells. Bone 27(2)  :  233–239PubMedCrossRefGoogle Scholar
  155. Zayzafoon M, Gathings WE, McDonald JM (2004) Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology 145(5)  :  2421–2432PubMedCrossRefGoogle Scholar
  156. Zerath E, Holy X, Noël B, Malouvier A, Hott M, Marie PJ (1998) Effects of BMP-2 on osteoblastic cells and on skeletal growth and bone formation in unloaded rats. Growth Horm IGF Res 8(2)  :  141–149PubMedCrossRefGoogle Scholar
  157. Zhang R, Supowit SC, Klein GL, Lu Z, Christiensen MD, Lozano R, Simmons DJ (1995) Rat tail suspension reduces messenger RNA level for growth factors and osteopontin and decreases the osteoblastic differentiation of bone marrow stromal cells. J Bone Miner Res 10  :  415–423PubMedCrossRefGoogle Scholar
  158. Ziambaras K, Lecanda F, Steinberg TH, Civitelli R (1998) Cyclic stretch enhances gap junctional communication between osteoblastic cells. J Bone Miner Res 13(2)  :  218–228PubMedCrossRefGoogle Scholar
  159. Ziros PG, Gil AP, Georgakopoulos T, Habeos I, Kletsas D, Basdra EK, Papavassiliou AG (2002) The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. J Biol Chem 277(26)  :  23934–23941PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Laboratory of Osteoblast Biology and PathologyInserm U606Paris Cedex 10France
  2. 2.University Paris DiderotParisFrance

Personalised recommendations