Skip to main content
SpringerLink
Log in

Effects of Microgravity on Skeletal Remodeling and Bone Cells

  • Chapter
The Skeleton

Abstract

The skeleton is a complex living tissue that serves multiple functions, such as mechanical support of the body, protection of the vital organs, and reservoir of minerals. Gravity and loading exert important effects on the skeleton because they control bone mass. Consistently, unloading and microgravity induce multiple alterations in bone cell function and skeletal structure. This chapter, summarizes the effects of microgravity on bone metabolism and the most recent informations on the cellular and molecular mechanisms that might be involved in the effects of loading and unloading on bone cells.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. de Vernejoul, M. C. and Marie, P. J. (2001) New aspects of bone biology, in Spectrum of Renal Osteodystrophy (Drueke, T. and Salusky, I. B., eds.). Oxford University Press. Oxford. pp. 3–22.

    Google Scholar 

  2. Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M. T., and Martin, T. J. (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr. Rev 20, 345–357

    Article  PubMed  CAS  Google Scholar 

  3. Baron, R. (1996) Molecular mechanisms of bone resorption: therapeutic implications. Rev. Rhum. Engl. Ed. 63, 633–638.

    PubMed  CAS  Google Scholar 

  4. Karsenty, G. (2001) Minireview: transcriptional control of osteoblast differentiation. Endocrinology 142, 2731–2733.

    Article  PubMed  CAS  Google Scholar 

  5. Marie, P. J. (1999) Osteoblasts and bone formation, in Advances in Organ Biology: Molecular and Cellular Biology of Bone Vol. 5B (Zaidi, M.. ed.). JAI Press. Stamford. CT. p. 401–427.

    Google Scholar 

  6. Frost, H. M., Ferretti, J. L., and Jee, W. S. (1998) Perspectives: some roles of mechanical usage, muscle strength, and the mechanostat in skeletal physiology, disease, and research. Calcif. Tissue Int. 62. 1–7.

    Article  PubMed  CAS  Google Scholar 

  7. Sheng, M. H., Baylink, D. J., Beamer, W. G., Donahue, L. R., Rosen, C. J., Lau, K. H., et al. (1999) Histomorphometric studies show that bone formation and bone mineral apposition rates are greater in C3H/HeJ (high-density) than C57BL/6J (low-density) mice during growth. Bone 25, 421–429.

    Article  PubMed  CAS  Google Scholar 

  8. Marie, P. J. (2001) The molecular genetics of bone formation: implications for therapeutic interventions in bone disorders. Am. J. Pharmacogenomics 1, 175–187.

    Article  PubMed  CAS  Google Scholar 

  9. Eisman, J. A. (1999) Genetics of osteoporosis. Endocr. Rev. 20, 788–804.

    Article  PubMed  CAS  Google Scholar 

  10. Ralston, S. H. (2001) Genetics of osteoporosis. Rev. Endocr. Metab. Disord. 2, 13–21.

    Article  PubMed  CAS  Google Scholar 

  11. Landis, W. J. (1999) An overview of vertebrate mineralization with emphasis on collagen-mineral interaction. Gravit. Space Biol. Bull. 12, 15–26.

    PubMed  CAS  Google Scholar 

  12. Robling, A. G., Duijvelaar, K. M., Geevers, J. V., Ohashi, N., and Turner, C. H. (2001) Modulation of appositional and longitudinal bone growth in the rat ulna by applied static and dynamic force. Bone 29. 105–113.

    Article  PubMed  CAS  Google Scholar 

  13. Rubin, C., Turner, A. S., Bain, S., Mallinckrodt, C., and McLeod, K. (2001) Anabolism. Low mechanical signals strengthen long bones. Nature 412, 603–604.

    Article  PubMed  CAS  Google Scholar 

  14. Krall, E. A. and Dawson-Hughes, B. (1994) Walking is related to bone density and rates of bone loss. Am. J. Med. 96, 20–26.

    Article  PubMed  CAS  Google Scholar 

  15. Zerath, E. (1998) Effects of microgravity on bone and calcium homeostasis. Adv. Space Res. 21, 1049–1058.

    Article  PubMed  CAS  Google Scholar 

  16. Vico, L. M., Hinsenkamp, D., Jones Marie, P. J., Zallone, A., and Cancedda, R. (2001) Osteobiology, strain and microgravity. Part II: studies at the tissue level. Calcif. Tissue Int. 68, 1–10.

    Article  PubMed  CAS  Google Scholar 

  17. Smith, S. M., Nillen, J. L., Leblanc, A., Lipton, A., Demers, L. M., Lane, H. W., et al. (1998) Collagen cross-link excretion during space flight and bed rest. J. Clin. Endocrinol. Metab. 83, 3584–3591.

    Article  PubMed  CAS  Google Scholar 

  18. Caillot-Augusseau, A., Lafage-Proust, M. H., Soler, C., Pernod, J., Dubois, F., and Alexandre, C. (1998) Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95). Clin. Chem. 44, 578–585.

    PubMed  CAS  Google Scholar 

  19. Morey-Holton, E. R. and Globus, R. K. (1998) Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight. Bone 22, 83S–88S.

    Article  PubMed  CAS  Google Scholar 

  20. Zerath, E., Holy, X., Roberts, S. G., Andre, C., Renault, S., Hott, M., et al. (2000) Spaceflight inhibits bone formation independent of corticosteroid status in growing rats. J. Bone Miner. Res. 15, 1310–1320.

    Article  PubMed  CAS  Google Scholar 

  21. Marie, P. J., Jones, D., Vico, L., Zallone, A., Hinsenkamp, M., and Cancedda, R. (2000) Osteobiology, strain, and microgravity: part, I. Studies at the cellular level. Calcif. Tissue Int. 67, 2–9.

    Article  PubMed  CAS  Google Scholar 

  22. Burger, E. H. and Klein-Nulend, J. (1998) Microgravity and bone cell mechanosensitivity. Bone 22, 127S–130S.

    Article  PubMed  CAS  Google Scholar 

  23. Landis, W. J., Hodgens, K. J., Block, D., Toma, C. D., and Gerstenfeld, L. C. (2000) Spaceflight effects on cultured embryonic chick bone cells. J. Bone Miner. Res. 15, 1099–1112.

    Article  PubMed  CAS  Google Scholar 

  24. Guignandon, A., Usson, Y., Laroche, N., Lafage-Proust, M. H., Sabido, O., Alexandre, C., et al. (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. 66–75.

    Article  PubMed  CAS  Google Scholar 

  25. Rucci, N., Migliaccio, S., Zani, B. M., Taranta, A., and Teti, A. (2002) Characterization of the osteoblast-like cell phenotype under microgravity conditions in the NASA-approved Rotating Wall Vessel bioreactor (RWV). J. Cell. Biochem. 85, 167–179.

    Article  PubMed  CAS  Google Scholar 

  26. Jee, W. S. and Ma, Y. (1999) Animal models of immobilization osteopenia. Morphologie 83, 25–34.

    PubMed  CAS  Google Scholar 

  27. Zerwekh, J. E., Ruml, L. A., Gottschalk, F., and Pak, C. Y. (1998) The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J. Bone Miner. Res. 13, 1594–1601.

    Article  PubMed  CAS  Google Scholar 

  28. Inoue, M., Tanaka, H., Moriwake, T., Oka, M., Sekiguchi, C., and Seino, Y. (2000) Altered biochemical markers of bone turnover in humans during 120 days of bed rest. Bone 26, 281–286.

    Article  PubMed  CAS  Google Scholar 

  29. Palle, S., Vico, L., Bourrin, S., and Alexandre, C. (1992) Bone tissue response to four-month antiorthostatic bedrest: a bone histomorphometric study. Calcif. Tissue Int. 51, 189–194.

    Article  PubMed  CAS  Google Scholar 

  30. Wronski, T. J. and Morey-Holton, E. R. (1987) Skeletal response to simulated weightlessness: a comparison at suspension techniques. Aviat. Space Environ. Med. 58, 63–68.

    PubMed  CAS  Google Scholar 

  31. Sakata, T., Sakai, A., Tsurukami, H., Okimoto, N., Okazaki, Y., Ikeda, S., et al. (1999) Trabecular bone turnover and bone marrow cell development in tail-suspended mice. J. Bone Miner. Res. 14, 1596–1604.

    Article  PubMed  CAS  Google Scholar 

  32. Machwate, M., Zerath, E., Holy, X., Hott, M., Modrowski, D., Malouvier, A., et al. (1993) Skeletal unloading in rat decreases proliferation of rat bone and marrow-derived osteoblastic cells. Am. J. Physiol. 264, E790–E799.

    PubMed  CAS  Google Scholar 

  33. Ahdjoudj, S., Lasmoles, F., Holy, X., Zerath, E., and Marie, P. J. (2002) Transforming growth factor beta2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma. J. Bone Miner. Res. 17, 668–677.

    Article  PubMed  CAS  Google Scholar 

  34. Colleran, P. N., Wilkerson, M. K., Bloomfield, S. A., Suva, L. J., Turner, R. T., and Delp, M. D. (2000) Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling. J. Appl. Physiol. 89, 1046–1054.

    PubMed  CAS  Google Scholar 

  35. Marie, P. J. and Zerath, E. (2000) Role of growth factors in osteoblast alterations induced by skeletal unloading in rats. Growth Factors 18, 1–10.

    Article  PubMed  CAS  Google Scholar 

  36. Zhang, R., Supowit, S. C., Klein, G. L., Lu, Z., Christensen, M. D., Lozano, R., et al. (1995) Rat tail suspension reduces messenger RNA level for growth factors and osteopontin and decreases the osteoblastic bone differentiation of bone marrow stromal cells. J. Bone Miner. Res. 10, 415–423.

    Article  PubMed  CAS  Google Scholar 

  37. Kumei, Y., Nakamura, H., Morita, S., Akiyama, H., Hirano, M., Ohya, K., et al. (2002) Space flight and insulin-like growth factor-I signaling in rat osteoblasts. Ann. NY Acad. Sci. 973, 75–78.

    Article  PubMed  CAS  Google Scholar 

  38. Drissi, H., Lomri, A., Lasmoles, F., Holy, X., Zerath, E., and Marie, P. J. (1999) Skeletal unloading induces biphasic changes in insulin-like growth factor-I mRNA levels and osteoblast activity. Exp. Cell Res. 251, 275–284.

    Article  PubMed  CAS  Google Scholar 

  39. Machwate, M., Zerath, E., Holy, X., Pastoureau, P., and Marie, P. J. (1994) Insulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats. Endocrinology 134, 1031–1038.

    Article  PubMed  CAS  Google Scholar 

  40. Westerlind, K. C. and Turner, R. T. (1995) The skeletal effects of spaceflight in growing rats: tissue-specific alterations in mRNA levels for TGF-beta. J. Bone Miner. Res. 10, 843–848.

    Article  PubMed  CAS  Google Scholar 

  41. Machwate, M., Zerath, E., Holy, X., Hott, M., Godet, D., Lomri, A., and Marie, P. J. (1995) Systemic administration of transforming growth factor-beta 2 prevents the impaired bone formation and osteopenia induced by unloading in rats. J. Clin. Invest. 96, 1245–1253.

    Article  PubMed  CAS  Google Scholar 

  42. Turner, R. L., Evans, G. L., Cavolina, J. M., Halloran, B., and Morey-Holton, E. (1998) Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats. Fnndncrinolngv 139, 4086–4091.

    CAS  Google Scholar 

  43. Kodama, Y., Nakayama, K., Fuse, H., Fukumoto, S., Kawahara, H., Takahashi, H., et al. (1997) Inhibition of bone resorption by pamidronate cannot restore normal gain in cortical bone mass and strength in tail-suspended rapidly growing rats. J. Bone Miner. Res. 12, 1058–1067.

    Article  PubMed  CAS  Google Scholar 

  44. Bateman, T. A., Dunstan, C. R., Ferguson, V. L., Lacey, D. L., Ayers, R. A., and Simske, S. J. (2000) Osteoprotegerin mitigates tail suspension-induced osteopenia. Bone 26, 443–449.

    Article  PubMed  CAS  Google Scholar 

  45. Duncan, R. L. and Turner, C. H. (1995) Mechanotransduction and the functional response of bone to mechanical strain. Calcif. Tissue Int. 57, 344–358.

    Article  PubMed  CAS  Google Scholar 

  46. Cowin, S. C. (1998) On mechanosensation in bone under microgravity. Bone 22, 119S–125S.

    Article  PubMed  CAS  Google Scholar 

  47. Jones, D., Leivseth, G., and Tenbosch, J. (1995) Mechano-reception in osteoblast-like cells. Biochem. Cell Biol. 73, 525–534.

    Article  PubMed  CAS  Google Scholar 

  48. Guignandon, A., Usson, Y., Laroche, N., Lafage-Proust, M. H., Sabido, O., Alexandre, C., and Vico, L. (1997) Effects of intermittent or continuous gravitational stresses on cell-matrix adhesion: quantitative analysis of focal contacts in osteoblastic RUS 17/2.8 cells. Exp. Cell Res. 236, 66–75.

    Google Scholar 

  49. Hasegawa, S., Sato, S., Saito, S., Suzuki, Y., and Brunette, D. M. (1985) Mechanical stretching increases the number of cultured bone cells synthesizing DNA and alters their pattern of protein synthesis. Calcif. Tissue Int. 37, 431–436.

    Article  PubMed  CAS  Google Scholar 

  50. Ozawa, H., Imamura, K., Abe, E., Takahashi, N., Hiraide, T., Shibasaki, Y., et al. (1990) Effect of a continuously annlied comnressive pressure on mouse osteoblast-like cells (MC3T3-E1) in vitro. J. Cell Physiol. 142, 177–185.

    Article  PubMed  CAS  Google Scholar 

  51. Raab-Cullen, D. M., Thiede, M. A., Petersen, D. N., Kimmel, D. B., and Recker, R. R. (1994) Mechanical loading stimulates rapid changes in periosteal gene expression. Calcif. Tissue Int. 55, 473–478.

    Article  PubMed  CAS  Google Scholar 

  52. Harter, L. V., Hruska, K. A., and Duncan, R. L. (1995) Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. Endocrinology 136, 528–535.

    Article  PubMed  CAS  Google Scholar 

  53. Sarkar, D., Nagaya, T., Koga, K., Nomura, Y., Gruener, R., and Seo, H. (2000) Culture in vector-averaged gravity under clinostat rotation results in apoptosis of osteoblastic ROS 17/2.8 cells. J. Bone Miner. Res. 15, 489–498.

    Article  PubMed  CAS  Google Scholar 

  54. Rawlinson, S. C., Mosley, J. R., Suswillo, R. F., Pitsillides, A. A., and Lanyon, L. E. (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, 1225–1232.

    Article  PubMed  CAS  Google Scholar 

  55. Burger, E. H., Klein-Nulend, J., van der Plas, A., and Nijweide, P. J. (1995) Function of osteocytes in bone—their role in mechanotransduction. J. Nutr. 125(7 Suppl), 2020S–2023S.

    PubMed  CAS  Google Scholar 

  56. Burger, E. H. and Klein-Nulend, J. (1999) Mechanotransduction in bone—role of the lacuno-canalicular network. FASEB J. 13(Suppl), S101–S112.

    PubMed  CAS  Google Scholar 

  57. Chen, K. D., Li, Y. S., Kim, M., Li, S., Yuan, S., Chien, S., and Shyy, J. Y. (1999) Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J. Biol. Chem. 274. 18393–18400.

    Article  PubMed  CAS  Google Scholar 

  58. Lacouture, M. E., Schaffer, J. L., and Klickstein, L. B. (2002) A comparison of type I collagen, fibronectin, and vitronectin in supporting adhesion of mechanically strained osteoblasts. J. Bone Miner. Res. 17. 481–492.

    Article  PubMed  CAS  Google Scholar 

  59. Carvalho, R. S., Bumann, A., Schaffer, J. L., and Gerstenfeld, L. C. (2002) Predominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation. J. Cell Biochem. 84, 497–508.

    Article  PubMed  CAS  Google Scholar 

  60. Pommerenke, H., Schmidt, C., Durr, F., Nebe, B., Luthen, F., Muller, P., and Rychly, J. (2002) The mode of mechanical integrin stressing controls intracellular signaling in osteoblasts. J. Bone Miner. Res. 17, 603–611.

    Article  PubMed  CAS  Google Scholar 

  61. Ajubi, N. E., Klein-Nulend, J., Alblas, M. J., Burger, E. H., and Nijweide, P. J. (1999) Signal transduction pathways involved in fluid flow-induced PGE2 production by cultured osteocytes. Am. J. Physiol. 276(1 Pt 1). E171–E178.

    PubMed  CAS  Google Scholar 

  62. Pavalko, F. M., Chen, N. X., Turner, C. H., Burr, D. B., Atkinson, S., Hsieh, Y. F., et al. (1998) Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. Am. J. Physiol. 275(6 Pt 1), C1591–C1601.

    PubMed  CAS  Google Scholar 

  63. Salter, D. M., Robb, J. E., and Wright, M. O. (1997) Electrophysiological responses of human bone cells to mechanical stimulation: evidence for specific integrin function in mechanotransduction. J. Bone Miner. Res. 12, 1133–1141.

    Article  PubMed  CAS  Google Scholar 

  64. Carvalho, R. S., Schaffer, J. L., and Gerstenfeld, L. C. (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, 376–390.

    Article  PubMed  CAS  Google Scholar 

  65. Li, J., Duncan, R. L., Burr, D. B., and Turner, C. H. (2002) L-type calcium channels mediate mechanically induced bone formation in vivo. J. Bone Miner. Res. 17, 1795–1800.

    Article  PubMed  CAS  Google Scholar 

  66. Sackin, H. (1995) Stretch-activated ion channels. Kidney Int. 48, 1134–1147.

    Article  PubMed  CAS  Google Scholar 

  67. Duncan, R. L. and Hruska, K. A. (1994) Chronic, intermittent loading alters mechanosensitive channel characteristics in osteoblast-like cells. Am. J. Physiol. 267, F909–F916.

    PubMed  CAS  Google Scholar 

  68. Mason, D. J., Suva, L. J., Genever, P. G., Patton, A. J., Steuckle, S., Hillam, R. A., and Skerry, T. M. (1997) Mechanically regulated expression of a neural glutamate transporter in bone: a role for excitatory amino acids as osteotropic agents? Bone 20, 199–205.

    Article  PubMed  CAS  Google Scholar 

  69. Ziambaras, K., Lecanda, F., Steinberg, T. H., and Civitelli, R. (1998) Cyclic stretch enhances gap junctional communication between osteoblastic cells. J. Bone Miner. Res. 13. 218–228.

    Article  PubMed  CAS  Google Scholar 

  70. Westerlind, K. C., Wronski, T. J., Ritman, E. L., Luo, Z. P., An, K. N., Bell, N. H., et al. (1997) Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain. Proc. Natl. Acad. Sci. USA 94, 4199–4204.

    Article  PubMed  CAS  Google Scholar 

  71. Cheng, M. Z., Zaman, G., and Lanyon, L. E. (1994) Estrogen enhances the stimulation of bone collagen synthesis by loading and exogenous prostacyclin, but not prostaglandin E2, in organ cultures of rat ulnae. J. Bone Miner. Res. 9, 805–816.

    Article  PubMed  CAS  Google Scholar 

  72. Zaman, G., Cheng, M. Z., Jessop, H. L., White, R., and Lanyon, L. E. (2000) Mechanical strain activates estrogen response elements in bone cells. Bone 27, 233–239.

    Article  PubMed  CAS  Google Scholar 

  73. Cheng, M. Z., Rawlinson, S. C., Pitsillides, A. A., Zaman, G., Mohan, S., Baylink, D. J., et al. (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. 593–602

    Article  PubMed  CAS  Google Scholar 

  74. Jessop, H. L., Sjoberg, M., Cheng, M. Z., Zaman, G., Wheeler-Jones, C. P., and Lanyon, L. E. (2001) Mechanical strain and estrogen activate estrogen receptor alpha in bone cells. J. Bone Miner. Res. 16, 1045–1055.

    Article  PubMed  CAS  Google Scholar 

  75. Lee, K., Jessop, H., Suswillo, R., Zaman, G., and Lanyon, L. (2003) Endocrinology: bone adaptation requires oestrogen receptor-aloha. Nature 424, 389

    Article  PubMed  CAS  Google Scholar 

  76. Carvalho, R. S., Scott, J. E., Suga, D. M., and Yen, E. H. (1994) Stimulation of signal transduction pathways in osteoblasts by mechanical strain potentiated by parathyroid hormone. J. Bone Miner. Res. 9, 999–1011.

    Article  PubMed  CAS  Google Scholar 

  77. Rubin, J., Murphy, T. C., Fan, X., Goldschmidt, M., and Taylor, W. R. (2002) Activation of extracellular signalregulated kinase is involved in mechanical strain inhibition of RANKL expression in bone stromal cells. J. Bone Miner. Res. 17, 1452–1460.

    Article  PubMed  CAS  Google Scholar 

  78. Geng, W. D., Boskovic, G., Fultz, M. E., Li, C., Niles, R. M., Ohno, S., and Wright, G. L. (2001) Regulation of expression and activity of four PKC isozymes in confluent and mechanically stimulated UMR-108 osteoblastic cells. J. Cell Physiol. 189, 216–228.

    Article  PubMed  CAS  Google Scholar 

  79. You, J., Reilly, G. C., Zhen, X., Yellowley, C. E., Chen, Q., Donahue, H. J., and Jacobs, C. R. (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, 13365–13371.

    Article  PubMed  CAS  Google Scholar 

  80. Klein-Nulend, J., Burger, E. H., Semeins, C. M., Raisz, L. G., and Pilbeam, C. C. (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, 45–51.

    Article  PubMed  CAS  Google Scholar 

  81. Cheng, B., Kato, Y., Zhao, S., Luo, J., Sprague, E., Bonewald, L. F., and Jiang, J. X. (2001) PGE(2) is essential for gap junction-mediated intercellular communication between osteocyte-like MLO-Y4 cells in response to mechanical strain. Endocrinology 142, 3464–3473.

    Article  PubMed  CAS  Google Scholar 

  82. Binderman, I., Shimshoni, Z., and Somjen, D. (1984) Biochemical pathways involved in the translation of physical stimulus into biological message. Calcif. Tissue Int. 36(Suppl 1), S82–S85.

    Article  PubMed  Google Scholar 

  83. van’t Hof, R. J. and Ralston, S. H. (2001) Nitric oxide and bone. Immunology 103, 255–261.

    Article  PubMed  Google Scholar 

  84. Klein-Nulend, J., Semeins, C. M., Ajubi, N. E., Nijweide, P. J., and Burger, E. H. (1995) Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts—correlation with prostaglandin upregulation. Biochem. Biophys. Res. Commun. 217, 640–648.

    Article  PubMed  CAS  Google Scholar 

  85. Wadhwa, S., Godwin, S. L., Peterson, D. R., Epstein, M. A., Raisz, L. G., and Pilbeam, C. C. (2002) Fluid flow induction of cyclo-oxygenase 2 gene expression in osteoblasts is dependent on an extracellular signal-regulated kinase sienaling Pathway. J. Bone Miner. Res. 17, 266–274.

    Article  PubMed  CAS  Google Scholar 

  86. Ogasawara, A., Arakawa, T., Kaneda, T., Takuma, T., Sato, T., Kaneko, H., et al. (2001) Fluid shear stress-induced cyclooxygenase-2 expression is mediated by C/EBP beta, cAMP-response element-binding protein, and AP-1 in osteoblastic MC3T3-E1 cells. J. Biol. Chem. 276, 7048–7054.

    Article  PubMed  CAS  Google Scholar 

  87. Reich, K. M. and Frangos, J. A. (1991) Effect of flow on prostaglandin E2 and inositol trisphosphate levels in osteoblasts. Am. J. Physiol. 261, C428–C432.

    PubMed  CAS  Google Scholar 

  88. Kawata, A. and Mikuni-Takagaki, Y. (1998) Mechanotransduction in stretched osteocytes—temporal expression of immediate early and other genes. Biochem. Biophys. Res. Commun. 246, 404–408.

    Article  PubMed  CAS  Google Scholar 

  89. Nomura, S. and Takano-Yamamoto, T. (2000) Molecular events caused by mechanical stress in bone. Matrix Biol. 19, 91–96.

    Article  PubMed  CAS  Google Scholar 

  90. Peake, M. A., Cooling, L. M., Magnay, J. L., Thomas, P. B., and El Haj, A. J. (2000) Selected contribution: regulatory pathways involved in mechanical induction of c-fos gene expression in bone cells. J. Appl. Physiol. 89, 2498–2507.

    PubMed  CAS  Google Scholar 

  91. Mikuni-Takagaki, Y. (1999) Mechanical responses and signal transduction pathways in stretched osteocytes. J. Bone Miner. Metab. 17, 57–60.

    Article  PubMed  CAS  Google Scholar 

  92. Kletsas, D., Basdra, E. K., and Papavassiliou, A. G. (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, 313–321.

    Article  PubMed  CAS  Google Scholar 

  93. Granet, C., Vico, A. G., Alexandre, C., and Lafage-Proust, M. H. (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, 679–688.

    Article  PubMed  CAS  Google Scholar 

  94. Sakai, A., Sakata, T., Tanaka, S., Okazaki, R., Kunugita, N., Norimura, T., and 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, 119–127.

    Article  PubMed  CAS  Google Scholar 

  95. Ziros, P. G., Gil, A. P., Georgakopoulos, T., Habeos, I., Kletsas, D., Basdra, E. K., et al. (2002) The bone-specific transcriptional reeulator Cbfa 1 is a target of mechanical signals in osteoblastic cells. J. Biol. Chem. 277, 23934–23941.

    Article  PubMed  CAS  Google Scholar 

  96. Ontiveros, C., and McCabe, L. R. (2003) Simulated microgravity suppresses osteoblast phenotype, Runx2 levels and AP-1 transactivation. J. Cell Biochem. 88, 427–437.

    Article  PubMed  CAS  Google Scholar 

  97. Westerlind, K. C., Morey-Holton, E., Evans, G. L., Tanner, S. J., and Turner, R. T. (1996) TGF-13 may help couple mechanical strain and bone cell activity in vivo. J. Bone Miner. Res. 11, 5:377.

    Google Scholar 

  98. Klein-Nulend, J., Roelofsen, J., Sterck, J. G., Semeins, C. M., and Burger, E. H. (1995) Mechanical loading stimulates the release of transforming growth factor- beta activity by cultured mouse calvariae and periosteal cells. J. Cell Physiol. 163, 115–119.

    Article  PubMed  CAS  Google Scholar 

  99. Sakai, K., Mohtai, M., and Iwamoto, Y. (1998) Fluid shear stress increases transforming growth factor beta 1 expression in human osteoblast-like cells: modulation by cation channel blockades. Tissue Int. 63, 515–520.

    Article  CAS  Google Scholar 

  100. Zhuang, H., Wang, W., Tahernia, A. D., Levitz, C. L., Luchetti, W. T., and Brighton, C. T. (1996) Mechanical straininduced proliferation of osteoblastic cells parallels increased TGF-beta 1 mRNA. Biochem. Biophys. Res. Commun. 229, 449–453.

    Article  PubMed  CAS  Google Scholar 

  101. Kumei, Y., Shimokawa, H., Katano, H., Hara, E., Akiyama, H., Hirano, M., et al. (1996) Microgravity induces prostaglandin E2 and interleukin-6 production in normal rat osteoblasts: role in bone demineralization. J. Biotechnol. 47, 313–324.

    Article  PubMed  CAS  Google Scholar 

  102. Grano, M., Mori, G., Minielli, V., Barou, O., Colucci, S., Giannelli, G., et al. (2002) Rat hindlimb unloading by tail suspension reduces osteoblast differentiation, induces IL-6 secretion, and increases bone resorption in ex vivo cultures. Tissue Int. 70, 176–185.

    Article  CAS  Google Scholar 

  103. Kanematsu, M., Yoshimura, K., Takaoki, M., and 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, 553–558.

    Article  PubMed  CAS  Google Scholar 

  104. Rubin, J., Murphy, T., Nanes, M. S., and Fan, X. (2000) Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells. Am. J. Phvsiol. Cell Physiol. 278, C1126–C1132.

    CAS  Google Scholar 

  105. Backup, P., Westerlind, K.. Harris, S., Spelsberg, T., Kline, B., and Turner, R. (1994) Spaceflight results in reduced mRNA levels for tissue-specific proteins in the musculoskeletal system. Am. J. Physiol. 266, E567–E573.

    PubMed  CAS  Google Scholar 

  106. Bikle, D. D. Harris, J., Halloran, B. P., and Morey-Holton, E. (1994) Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation. Am. J. Physiol. 267, E822–E827.

    PubMed  CAS  Google Scholar 

  107. Cavolina, J. M., Evans, G. L., Harris, S. A., Zhang, M.. Westerlind, K. C., and Turner, R. T. (1997) The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats. Endocrinology 138, 1567–1576.

    Article  PubMed  CAS  Google Scholar 

  108. Carmeliet, G., Nys, G., and Bouillon, R. (1997) Microgravity reduces the differentiation of human osteoblastic MG63 cells. J. Bone Miner. Res. 12, 786–794.

    Article  PubMed  CAS  Google Scholar 

  109. Harter, L. V., Hruska, K. A., and Duncan, R. L. (1995) Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. Endocrinology 136, 528–535.

    Article  PubMed  CAS  Google Scholar 

  110. Toma, C. D., Ashkar, S., Gray, M. L., Schaffer, J. L., and Gerstenfeld, L. C. (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, 1626–1636.

    Article  PubMed  CAS  Google Scholar 

  111. Terai, K., Takano-Yamamoto, T., Ohba, Y., Hiura, K., Sugimoto, M., Sato, M., et al. (1999) Role of osteopontin in bone remodeling caused by mechanical stress. J. Bone Miner. Res. 14, 839–849.

    Article  PubMed  CAS  Google Scholar 

  112. Morinobu, M., Ishijima, M., Rittling, S. R., Tsuji, K., Yamamoto, H., Nifuji, A., et al. (2003) Osteopontin expression in osteoblasts and osteocytes during bone formation under mechanical stress in the calvarial suture in vivo. J. Bone Miner. Res. 18. 706–715.

    Article  Google Scholar 

  113. Carvalho, R. S., Bumann, A., Schaffer, J. L., and Gerstenfeld, L. C. (2002) Predominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation. J. Cell Biochem. 84, 497–508.

    Article  PubMed  CAS  Google Scholar 

  114. Ishijima, M., Rittling, S. R., Yamashita, T., Tsuji, K., Kurosawa, H., Nifuji, A., Denhardt, D. T., and 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, 399–404.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Pierre J. Marie
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Developmental Biology Branch, Reproductive Toxicology Division, The National Health and Environmental Effects Research Laboratory, Office of Research Development, United States Environmental Protection Agency, Research Triangle Park, NC, USA

    Edward J. Massaro  & John M. Rogers  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Marie, P.J. (2004). Effects of Microgravity on Skeletal Remodeling and Bone Cells. In: Massaro, E.J., Rogers, J.M. (eds) The Skeleton. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-736-9_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-736-9_18

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-427-2

  • Online ISBN: 978-1-59259-736-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation