Annals of Biomedical Engineering

, Volume 36, Issue 12, pp 1978–1991 | Cite as

The Mechanical Environment of Bone Marrow: A Review

  • Umut Atakan Gurkan
  • Ozan AkkusEmail author


Bone marrow is a viscous tissue that resides in the confines of bones and houses the vitally important pluripotent stem cells. Due to its confinement by bones, the marrow has a unique mechanical environment which has been shown to be affected from external factors, such as physiological activity and disuse. The mechanical environment of bone marrow can be defined by determining hydrostatic pressure, fluid flow induced shear stress, and viscosity. The hydrostatic pressure values of bone marrow reported in the literature vary in the range of 10.7–120 mmHg for mammals, which is generally accepted to be around one fourth of the systemic blood pressure. Viscosity values of bone marrow have been reported to be between 37.5 and 400 cP for mammals, which is dependent on the marrow composition and temperature. Marrow’s mechanical and compositional properties have been implicated to be changing during common bone diseases, aging or disuse. In vitro experiments have demonstrated that the resident mesenchymal stem and progenitor cells in adult marrow are responsive to hydrostatic pressure, fluid shear or to local compositional factors such as medium viscosity. Therefore, the changes in the mechanical and compositional microenvironment of marrow may affect the fate of resident stem cells in vivo as well, which in turn may alter the homeostasis of bone. The aim of this review is to highlight the marrow tissue within the context of its mechanical environment during normal physiology and underline perturbations during disease.


Mesenchymal stem cells Marrow progenitor cells Physiological activity Osteoporosis Disuse Aging Pressure Fluid shear Rheology Viscosity 



We would like to acknowledge Dr. David C. Van Sickle for inspiring discussions and providing the histological figure of bone marrow; Sharon Evander and Carol Bain for their help in preparing the histological figure for publication.


  1. 1.
    Angele P., D. Schumann, M. Angele, B. Kinner, C. Englert, R. Hente, B. Fuchtmeier, M. Nerlich, C. Neumann, R. Kujat, 2004 Cyclic, mechanical compression enhances chondrogenesis of mesenchymal progenitor cells in tissue engineering scaffolds. Biorheology, 41(3–4):335–346PubMedGoogle Scholar
  2. 2.
    Angele P., J. U. Yoo, C. Smith, J. Mansour, K. J. Jepsen, M. Nerlich, B. Johnstone 2003 Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. Journal of Orthopaedic Research, 21(3):451–457.  10.1016/S0736-0266(02)00230-9 PubMedCrossRefGoogle Scholar
  3. 3.
    Azuma, H., Intraosseous Pressure as Measure of Hemodynamic Changes in Bone Marrow. Angiology, 1964. 15(9): p. 396-&. doi: 10.1177/000331976401500903 PubMedCrossRefGoogle Scholar
  4. 4.
    Balcells, M., M. F. Suarez, M. Vazquez, E. R. Edelman 2005 Cells in fluidic environments are sensitive to flow frequency. Journal of Cellular Physiology, 204(1):329–335.  10.1002/jcp.20281 PubMedCrossRefGoogle Scholar
  5. 5.
    Bauer, M. S., T. L. Walker 1988 Intramedullary pressure in canine long bones. American Journal of Veterinary Research, 49(3):425–427PubMedGoogle Scholar
  6. 6.
    Braccini A., D. Wendt, C. Jaquiery, M. Jakob, M. Heberer, L. Kenins, A. Wodnar-Filipowicz, R. Quarto, I. Martin, 2005 Three-dimensional perfusion culture of human bone marrow cells and generation of osteoinductive grafts. Stem Cells, 23(8):1066–1072.  10.1634/stemcells.2005-0002 PubMedCrossRefGoogle Scholar
  7. 7.
    Branemark P. I., 1959 Vital microscopy of bone marrow in rabbit. Scand J Clin Lab Invest, 11(Suppl 38):1–82.  10.3109/00365515909060400 PubMedGoogle Scholar
  8. 8.
    Bryant, J. D., The Effect of Impact on the Marrow Pressure of Long Bones Invitro. Journal of Biomechanics, 1983. 16(8): p. 659-&. doi: 10.1016/0021-9290(83)90117-3 PubMedCrossRefGoogle Scholar
  9. 9.
    Bryant J. D., 1995 On Hydraulic Strengthening of Bones. Journal of Biomechanics, 28(3):353–354.  10.1016/0021-9290(95)90563-L PubMedCrossRefGoogle Scholar
  10. 10.
    Bryant J. D., T. David, P. H. Gaskell, S. King, G. Lond, 1989 Rheology of bovine bone marrow. Proc Inst Mech Eng [H], 203(2):71–5.  10.1243/PIME_PROC_1989_203_013_01 Google Scholar
  11. 11.
    Burr D. B., A. G. Robling, C. H. Turner, 2002 Effects of biomechanical stress on bones in animals. Bone, 30(5):781–786.  10.1016/S8756-3282(02)00707-X PubMedCrossRefGoogle Scholar
  12. 12.
    Cabrita G. J. M., B. S. Ferreira, C. L. da Silva, R. Goncalves, G. Almeida-Porada, J. M. S. Cabral, 2003 Hematopoietic stem cells: from the bone to the bioreactor. Trends in Biotechnology, 21(5):233–240.  10.1016/S0167-7799(03)00076-3 PubMedCrossRefGoogle Scholar
  13. 13.
    Canalis E., 2005 The fate of circulating osteoblasts. New England Journal of Medicine, 352(19):2014–2016.  10.1056/NEJMe058080 PubMedCrossRefGoogle Scholar
  14. 14.
    Chen N. X., K. D. Ryder, F. M. Pavalko, C. H. Turner, D. B. Burr, J. Y. Qiu, R. L. Duncan, 2000 Ca2+ regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts. American Journal of Physiology-Cell Physiology, 278(5):C989-C997PubMedGoogle Scholar
  15. 15.
    Chen X., H. Xu, C. Wan, M. McCaigue, G. Li, 2006 Bioreactor expansion of human adult bone marrow-derived mesenchymal stem cells. Stem Cells, 24(9):2052–2059.  10.1634/stemcells.2005-0591 PubMedCrossRefGoogle Scholar
  16. 16.
    Courteix D., E. Lespessailles, S. L. Peres, P. Obert, P. Germain, C. L. Benhamou, 1998 Effect of physical training on bone mineral density in prepubertal girls: A comparative study between impact-loading and non-impact-loading sports. Osteoporosis International, 8(2):152–158.  10.1007/BF02672512 PubMedCrossRefGoogle Scholar
  17. 17.
    Davis, L. B., and S. S. Praveen. Nonlinear versus linear behavior of calcaneal bone marrow at different shear rates. In: American Society of Biomechanics Annual Meeting, Blacksburg, VA, 2006. Available from:
  18. 18.
    Dennis J. E., A. I. Caplan, 2003 Bone Marrow Mesenchymal Stem Cells. In S. Sell (Eds) Stem Cells Handbook. Humana Press Inc.: Totowa, NJ. p 107–118CrossRefGoogle Scholar
  19. 19.
    Dickerson, D. A., E. A. Sander, and E. A. Nauman. Modeling the mechanical consequences of vibratory loading in the vertebral body: microscale effects. Biomech. Model. Mechanobiol., 2007.Google Scholar
  20. 20.
    Dietz A. A., 1946 Composition of Normal Bone Marrow in Rabbits. Journal of Biological Chemistry, 165(2):505–511PubMedGoogle Scholar
  21. 21.
    Donahue T. L. H., T. R. Haut, C. E. Yellowley, H. J. Donahue, C. R. Jacobs, 2003 Mechanosensitivity of bone cells to oscillating fluid flow induced shear stress may be modulated by chemotransport. Journal of Biomechanics, 36(9):1363–1371.  10.1016/S0021-9290(03)00118-0 PubMedCrossRefGoogle Scholar
  22. 22.
    Donahue S. W., C. R. Jacobs, H. J. Donahue, 2001 Flow-induced calcium oscillations in rat osteoblasts are age, loading frequency, and shear stress dependent. American Journal of Physiology-Cell Physiology, 281(5):C1635–C1641PubMedGoogle Scholar
  23. 23.
    Downey D. J., P. A. Simkin, R. Taggart, 1988 The Effect of Compressive Loading on Intraosseous Pressure in the Femoral-Head Invitro. Journal of Bone and Joint Surgery-American Volume, 70A(6):871–877Google Scholar
  24. 24.
    Drinker C. K., K. R. Drinker, 1916 A Method for Maintaining an Artificial Circulation through the Tibia of the Dog, With a Demonstration of the Vasomotor Control of the Marrow Vessels. American Journal of Physiology, 40:514–521Google Scholar
  25. 25.
    Drinker C. K., K. R. Drinker, C. C. Lund, 1922 The circulation in the mammalian bone-marrow - With especial reference to the factors concerned in the movement of red blood cells from the bone marrow into the circulating blood as disclosed by perfusion of the tibia of the dog and by injections of the bone-marrow in the rabbit and cat. American Journal of Physiology, 62(1):1–92Google Scholar
  26. 26.
    Eguchi Y., T. Karino, 2008 Measurement of rheologic property of blood by a falling-ball blood viscometer. Annals of Biomedical Engineering, 36(4):545–553.  10.1007/s10439-008-9454-7 PubMedCrossRefGoogle Scholar
  27. 27.
    Estes B. T., J. M. Gimble, F. Guilak, 2004 Mechanical signals as regulators of stem cell fate. Stem Cells in Development and Disease, 60:91–126.  10.1016/S0070-2153(04)60004-4 CrossRefGoogle Scholar
  28. 28.
    Fox S. W., T. J. Chambers, J. W. M. Chow, 1996 Nitric oxide is an early mediator of the increase in bone formation by mechanical stimulation. American Journal of Physiology-Endocrinology and Metabolism, 33(6):E955–E960Google Scholar
  29. 29.
    Fox S. W., J. W. M. Chow, 1998 Nitric oxide synthase expression in bone cells. Bone, 23(1):1–6.  10.1016/S8756-3282(98)00070-2 PubMedCrossRefGoogle Scholar
  30. 30.
    Gimble J. M., C. E. Robinson, X. Wu, K. A. Kelly, 1996 The function of adipocytes in the bone marrow stroma: An update. Bone, 19(5):421–428.  10.1016/S8756-3282(96)00258-X PubMedCrossRefGoogle Scholar
  31. 31.
    Gurkan, U. A., and O. Akkus. An implantable magnetoelastic sensor system for wireless physiological sensing of viscosity. In: Proceeding of the ASME Summer Bioengineering Conference - 2007. New York: Amer. Soc. Mechanical Engineers, 2007, pp. 759–760Google Scholar
  32. 32.
    Harrelson, J. M., and B. A. Hills. Changes in bone marrow pressure in response to hyperbaric exposure. Aerospace Med. 41(9):1018–1021, 1970.Google Scholar
  33. 33.
    Huggins C., B. H. Blocksom, 1936 Changes in outlying bone marrow accompanying a local increase of temperature within physiological limits. Journal of Experimental Medicine, 64(2):253–U4.  10.1084/jem.64.2.253 CrossRefPubMedGoogle Scholar
  34. 34.
    Huggins C., B. H. Blocksom, W. J. Noonan, 1936 Temperature conditions in the bone marrow of rabbit, pigeon and albino rat. American Journal of Physiology, 115(2):395–401Google Scholar
  35. 35.
    Huggins C., W. J. Noonan, 1936 An increase in reticulo-endothelial cells in outlying bone marrow consequent upon a local increase in temperature. Journal of Experimental Medicine, 64(2):275-U7.  10.1084/jem.64.2.275 CrossRefPubMedGoogle Scholar
  36. 36.
    Hung C. T., S. R. Pollack, T. M. Reilly, C. T. Brighton, 1995 Real-Time Calcium Response of Cultured Bone-Cells to Fluid-Flow. Clinical Orthopaedics and Related Research, 313:256–269PubMedGoogle Scholar
  37. 37.
    Jacobs C. R., C. E. Yellowley, B. R. Davis, Z. Zhou, J. M. Cimbala, H. J. Donahue, 1998 Differential effect of steady versus oscillating flow on bone cells. Journal of Biomechanics, 31(11):969–976.  10.1016/S0021-9290(98)00114-6 PubMedCrossRefGoogle Scholar
  38. 38.
    Johnson D. L., T. N. McAllister, J. A. Frangos, 1996 Fluid flow stimulates rapid and continuous release of nitric oxide in osteoblasts. American Journal of Physiology-Endocrinology and Metabolism, 34(1):E205–E208Google Scholar
  39. 39.
    Justesen J., K. Stenderup, E. N. Ebbesen, L. Mosekilde, T. Steiniche, M. Kassem, 2001 Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology, 2(3):165–171.  10.1023/A:1011513223894 PubMedCrossRefGoogle Scholar
  40. 40.
    Kafka V., 1983 On Hydraulic Strengthening of Bones. Biorheology, 20(6):789–793PubMedGoogle Scholar
  41. 41.
    Kafka V., 1993 On Hydraulic Strengthening of Bones. Journal of Biomechanics, 26(6):761–762.  10.1016/0021-9290(93)90038-G PubMedCrossRefGoogle Scholar
  42. 42.
    Khademhosseini A., R. Langer, J. Borenstein, J. P. Vacanti, 2006 Microscale technologies for tissue engineering and biology. Proc Natl Acad Sci U S A, 103(8):2480–7.  10.1073/pnas.0507681102 PubMedCrossRefGoogle Scholar
  43. 43.
    KleinNulend J., C. M. Semeins, E. H. Burger, 1996 Prostaglandin mediated modulation of transforming growth factor-beta metabolism in primary mouse osteoblastic cells in vitro. Journal of Cellular Physiology, 168(1):1–7. doi:10.1002/(SICI)1097-4652(199607)168:1<1::AID-JCP1>3.0.CO;2-TCrossRefGoogle Scholar
  44. 44.
    Kleinnulend J., A. Vanderplas, C. M. Semeins, N. E. Ajubi, J. A. Frangos, P. J. Nijweide, E. H. Burger, 1995 Sensitivity of Osteocytes to Biomechanical Stress in-Vitro. Faseb Journal, 9(5):441–445Google Scholar
  45. 45.
    Krolner B., B. Toft, S. P. Nielsen, E. Tondevold, 1983 Physical Exercise as Prophylaxis against Involutional Vertebral Bone Loss - a Controlled Trial. Clinical Science, 64(5):541–546PubMedGoogle Scholar
  46. 46.
    Kumar S., P. R. Davis, B. Pickles, 1979 Bone-Marrow Pressure and Bone Strength. Acta Orthopaedica Scandinavica, 50(5):507–512PubMedCrossRefGoogle Scholar
  47. 47.
    Kuo C. K., W. J. Li, R. L. Mauck, R. S. Tuan, 2006 Cartilage tissue engineering: its potential and uses. Current Opinion in Rheumatology, 18(1):64–73.  10.1097/01.bor.0000198005.88568.df PubMedCrossRefGoogle Scholar
  48. 48.
    Kurokouchi K., C. R. Jacobs, H. J. Donahue, 2001 Oscillating fluid flow inhibits TNF-alpha-induced NF-kappa B activation via an I kappa B kinase pathway in osteoblast-like UMR106 cells. Journal of Biological Chemistry, 276(16):13499–13504.  10.1074/jbc.M003795200 PubMedCrossRefGoogle Scholar
  49. 49.
    Larsen R. M., 1938 Intramedullary pressure with particular reference to massive diaphyseal bone necrosis experimental observations. Annals of Surgery, 108:127–140.  10.1097/00000658-193807000-00009 PubMedCrossRefGoogle Scholar
  50. 50.
    Leblanc A. D., V. S. Schneider, H. J. Evans, D. A. Engelbretson, J. M. Krebs, 1990 Bone-Mineral Loss and Recovery after 17 Weeks of Bed Rest. Journal of Bone and Mineral Research, 5(8):843–850PubMedCrossRefGoogle Scholar
  51. 51.
    Li Y. J., N. N. Batra, L. D. You, S. C. Meier, I. A. Coe, C. E. Yellowley, C. R. Jacobs, 2004 Oscillatory fluid flow affects human marrow stromal cell proliferation and differentiation. Journal of Orthopaedic Research, 22(6):1283–1289.  10.1016/j.orthres.2004.04.002 PubMedCrossRefGoogle Scholar
  52. 52.
    Li J. L., D. W. Liu, H. Z. Ke, R. L. Duncan, C. H. Turner, 2005 The P2X(7) nucleotide receptor mediates skeletal mechanotransduction. Journal of Biological Chemistry, 280(52):42952–42959.  10.1074/jbc.M506415200 PubMedCrossRefGoogle Scholar
  53. 53.
    McAllister T. N., T. Du, J. A. Frangos, 2000 Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells. Biochemical and Biophysical Research Communications, 270(2):643–648.  10.1006/bbrc.2000.2467 PubMedCrossRefGoogle Scholar
  54. 54.
    McBeath R., D. M. Pirone, C. M. Nelson, K. Bhadriraju, C. S. Chen, 2004 Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Developmental Cell, 6(4):483–495.  10.1016/S1534-5807(04)00075-9 PubMedCrossRefGoogle Scholar
  55. 55.
    Michelsen, K., Pressure Relationships in Bone Marrow Vascular Bed. Acta Physiologica Scandinavica, 1967 71(1): p. 16-&PubMedGoogle Scholar
  56. 56.
    Michelsen K., 1968 Hemodynamics of the bone marrow circulation. Acta Physiol Scand, 73(3):264–80PubMedGoogle Scholar
  57. 57.
    Miyanishi K., M. C. D. Trindade, D. P. Lindsey, G. S. Beaupre, D. R. Carter, S. B. Goodman, D. J. Schurman, R. L. Smith, 2006 Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro. Tissue Engineering, 12(6):1419–1428.  10.1089/ten.2006.12.1419 PubMedCrossRefGoogle Scholar
  58. 58.
    Miyanishi K., M. C. D. Trindade, D. P. Lindsey, G. S. Beaupre, D. R. Carter, S. B. Goodman, D. J. Schurman, R. L. Smith, 2006 Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta 3-induced chondrogenesis by adult human mesenchymal stem cells in vitro. Tissue Engineering, 12(8):2253–2262.  10.1089/ten.2006.12.2253 PubMedCrossRefGoogle Scholar
  59. 59.
    Miyanishi K., T. Yamamoto, T. Irisa, A. Yamashita, S. Jingushi, Y. Noguchi, Y. Iwamoto, 2002 Bone marrow fat cell enlargement and a rise in Intraosseous pressure in steroid-treated rabbits with osteonecrosis. Bone, 30(1):185–190.  10.1016/S8756-3282(01)00663-9 PubMedCrossRefGoogle Scholar
  60. 60.
    Montgomery R. J., B. D. Sutker, J. T. Bronk, S. R. Smith, P. J. Kelly, 1988 Interstitial Fluid-Flow in Cortical Bone. Microvascular Research, 35(3):295–307.  10.1016/0026-2862(88)90084-2 PubMedCrossRefGoogle Scholar
  61. 61.
    Mori T., N. Okimoto, A. Sakai, Y. Okazaki, N. Nakura, T. Notomi, T. Nakamura, 2003 Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice. Journal of Bone and Mineral Research, 18(11):2002–2009.  10.1359/jbmr.2003.18.11.2002 PubMedCrossRefGoogle Scholar
  62. 62.
    Mori T., N. Okimoto, H. Tsurukami, A. Sakai, Y. Okazaki, S. Uchida, T. Notomi, T. Nakamura, 2001 Effects of tower climbing exercise on bone mass and turnover in growing mice. Journal of Bone and Mineral Research, 16(Suppl 1):S362Google Scholar
  63. 63.
    Nagatomi J., B. P. Arulanandam, D. W. Metzger, A. Meunier, R. Bizios, 2002 Effects of cyclic pressure on bone marrow cell cultures. Journal of Biomechanical Engineering-Transactions of the Asme, 124(3):308–314.  10.1115/1.1468867 CrossRefGoogle Scholar
  64. 64.
    Nagatomi J., B. R. Arulanandam, D. W. Metzger, A. Meunier, R. Bizios, 2003 Cyclic pressure affects osteoblast functions pertinent to osteogenesis. Annals of Biomedical Engineering, 31(8):917–923.  10.1114/1.1590663 PubMedCrossRefGoogle Scholar
  65. 65.
    Nakura N., T. Mori, N. Okimoto, A. Sakai, T. Nakamura, 2005 The climbing exercise prevents trabecular bone loss with highly expressed mRNA of estrogen receptor alpha in bone cells after ovariectomy in mice. Journal of Bone and Mineral Research, 20(9):S73–S73Google Scholar
  66. 66.
    Nauman E. A., R. L. Satcher, T. M. Keaveny, B. P. Halloran, D. D. Bikle, 2000 Osteoblasts in culture respond to in vitro pulsatile fluid flow with short term increases in PGE2 and long term increases in cell proliferation. Journal of Bone and Mineral Research, 15(Suppl 1):S500Google Scholar
  67. 67.
    Nauman E. A., R. L. Satcher, T. M. Keaveny, B. P. Halloran, D. D. Bikle, 2001 Osteoblasts respond to pulsatile fluid flow with shortterm increases in PGE(2) but no change in mineralization. Journal of Applied Physiology, 90(5):1849–1854PubMedGoogle Scholar
  68. 68.
    Nerlich M., D. Schumann, R. Kujat, P. Angele, 2004 Mechanobiological conditioning on mesenchymal stem cells during chondrogenesis. Shock, 21:136–136Google Scholar
  69. 69.
    Nesic D., R. Whiteside, M. Brittberg, D. Wendt, I. Martin, P. Mainil-Varlet, 2006 Cartilage tissue engineering for degenerative joint disease. Advanced Drug Delivery Reviews, 58(2):300–322.  10.1016/j.addr.2006.01.012 PubMedCrossRefGoogle Scholar
  70. 70.
    Ochoa J. A., A. P. Sanders, D. A. Heck, B. M. Hillberry, 1991 Stiffening of the Femoral-Head Due to Intertrabecular Fluid and Intraosseous Pressure. Journal of Biomechanical Engineering-Transactions of the Asme, 113(3):259–262.  10.1115/1.2894882 CrossRefGoogle Scholar
  71. 71.
    Ochoa J. A., A. P. Sanders, T. W. Kiesler, D. A. Heck, J. P. Toombs, K. D. Brandt, B. M. Hillberry, 1997 In vivo observations of hydraulic stiffening in the canine femoral head. Journal of Biomechanical Engineering-Transactions of the Asme, 119(1):103–108.  10.1115/1.2796051 CrossRefGoogle Scholar
  72. 72.
    Osteoporosis - Fast Facts. 2006, National Osteoporosis Foundation,
  73. 73.
    Petrakis N. L., 1952 Temperature of Human Bone Marrow. Journal of Applied Physiology, 4(7):549–553PubMedGoogle Scholar
  74. 74.
    Piekarski K., M. Munro, 1977 Transport Mechanism Operating between Blood-Supply and Osteocytes in Long Bones. Nature, 269(5623):80–82.  10.1038/269080a0 PubMedCrossRefGoogle Scholar
  75. 75.
    Pitsillides A. A., S. C. F. Rawlinson, R. F. L. Suswillo, G. Zaman, P. I. Nijweide, L. E. Lanyon, 1995 Mechanical Strain-Induced Nitric-Oxide Production by Osteoblasts and Osteocytes. Journal of Bone and Mineral Research, 10(Suppl 1):S217Google Scholar
  76. 76.
    Pittenger M. F., A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. D. Mosca, M. A. Moorman, D. W. Simonetti, S. Craig, D. R. Marshak, 1999 Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411):143–147.  10.1126/science.284.5411.143 PubMedCrossRefGoogle Scholar
  77. 77.
    Polak, J. M., and A. E. Bishop. Stem cells and tissue engineering: past, present, and future. Ann. NY Acad. Sci. 1068:352–366, 2006Google Scholar
  78. 78.
    Priller J., From Marrow to Brain. in Adult Stem Cells, K. Turksen Editor. 2004, Humana Press Inc.: Totowa, NJ. p. 215–233Google Scholar
  79. 79.
    Qin Y. X., T. Kaplan, A. Saldanha, C. Rubin, 2003 Fluid pressure gradients, arising from oscillations in intramedullary pressure, is correlated with the formation of bone and inhibition of intracortical porosity. Journal of Biomechanics, 36(10):1427–1437.  10.1016/S0021-9290(03)00127-1 PubMedCrossRefGoogle Scholar
  80. 80.
    Qin Y. X., W. Lin, C. Rubin, 2002 The pathway of bone fluid flow as defined by in vivo intramedullary pressure and streaming potential measurements. Annals of Biomedical Engineering, 30(5):693–702.  10.1114/1.1483863 PubMedCrossRefGoogle Scholar
  81. 81.
    Raisz L. G., 2005 Pathogenesis of osteoporosis: concepts, conflicts, and prospects. Journal of Clinical Investigation, 115(12):3318–3325.  10.1172/JCI27071 PubMedCrossRefGoogle Scholar
  82. 82.
    Reich K. M., J. A. Frangos, 1991 Effect of Flow on Prostaglandin-E2 and Inositol Trisphosphate Levels in Osteoblasts. American Journal of Physiology, 261(3):C428–C432PubMedGoogle Scholar
  83. 83.
    Reich K. M., T. N. Mcallister, S. Gudi, J. A. Frangos, 1997 Activation of G proteins mediates flow-induced prostaglandin E(2) production in osteoblasts. Endocrinology, 138(3):1014–1018.  10.1210/en.138.3.1014 PubMedCrossRefGoogle Scholar
  84. 84.
    Robling A. G., A. B. Castillo, C. H. Turner, 2006 Biomechanical and molecular regulation of bone remodeling. Annual Review of Biomedical Engineering, 8:455–498.  10.1146/annurev.bioeng.8.061505.095721 PubMedCrossRefGoogle Scholar
  85. 85.
    Rubin J., D. Biskobing, X. A. Fan, C. Rubin, K. McLeod, W. R. Taylor, 1997 Pressure regulates osteoclast formation and MCSF expression in marrow culture. Journal of Cellular Physiology, 170(1):81–87. 10.1002/(SICI)1097-4652(199701)170:1<81::AID-JCP9>3.0.CO;2-HPubMedCrossRefGoogle Scholar
  86. 86.
    Rubin J., C. Rubin, C. R. Jacobs, 2006 Molecular pathways mediating mechanical signaling in bone. Gene, 367:1–16.  10.1016/j.gene.2005.10.028 PubMedCrossRefGoogle Scholar
  87. 87.
    Schumann D., R. Kujat, M. Nerlich, P. Angele, 2006 Mechanobiological conditioning of stem cells for cartilage tissue engineering. Bio-Medical Materials and Engineering, 16(4):S37–S52PubMedGoogle Scholar
  88. 88.
    Semino, C.E., 2003 Can We Build Artificial Stem Cell Compartments? J Biomed Biotechnol, 2003(3), 164–169. doi: 10.1155/S1110724303208019 PubMedCrossRefGoogle Scholar
  89. 89.
    Sen A., M. S. Kallos, L. A. Behie, 2002 Expansion of mammalian neural stem cells in bioreactors: effect of power input and medium viscosity. Developmental Brain Research, 134(1–2):103–113.  10.1016/S0165-3806(01)00328-5 CrossRefGoogle Scholar
  90. 90.
    Shaw, N.E., Observations on Intramedullary Blood-Flow and Marrow-Pressure in Bone. Clinical Science, 1963. 24(3): p. 311-&PubMedGoogle Scholar
  91. 91.
    Shaw, N.E., Studies on Intramedullary Pressure + Blood Flow in Bone. American Heart Journal, 1964. 68(1): p. 134-&. doi: 10.1016/0002-8703(64)90250-9 PubMedCrossRefGoogle Scholar
  92. 92.
    Shim, S. S., W. Y. Yu, and H. E. Hawk. Relationship between blood-flow and marrow cavity pressure of bone. Surgery Gynecology and Obstetrics with International Abstracts of Surgery 135(3):353, 1972.Google Scholar
  93. 93.
    Sikavitsas V. I., G. N. Bancroft, H. L. Holtorf, J. A. Jansen, A. G. Mikos, 2003 Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces. Proceedings of the National Academy of Sciences of the United States of America, 100(25):14683–14688.  10.1073/pnas.2434367100 PubMedCrossRefGoogle Scholar
  94. 94.
    Sikavitsas V. I., G. N. Bancroft, J. J. Lemoine, M. A. K. Liebschner, M. Dauner, A. G. Mikos, 2005 Flow perfusion enhances the calcified matrix deposition of marrow stromal cells in biodegradable nonwoven fiber mesh scaffolds. Annals of Biomedical Engineering, 33(1):63–70.  10.1007/s10439-005-8963-x PubMedCrossRefGoogle Scholar
  95. 95.
    Simkin P. A., 2004 Hydraulically loaded the trabeculae may serve as springs within normal femoral head. Arthritis and Rheumatism, 50(10):3068–3075.  10.1002/art.20563 PubMedCrossRefGoogle Scholar
  96. 96.
    Stein A. H., H. C. Morgan, R. F. Porras, 1958 The Effect of Pressor and Depressor Drugs on Intramedullary Bone-Marrow Pressure. Journal of Bone and Joint Surgery-American Volume, 40(5):1103–1110PubMedGoogle Scholar
  97. 97.
    Stevens H. Y., D. R. Meays, J. A. Frangos, 2006 Pressure gradients and transport in the murine femur upon hindlimb suspension. Bone, 39(3):565–572.  10.1016/j.bone.2006.03.007 PubMedCrossRefGoogle Scholar
  98. 98.
    Stevens H. Y., D. R. Meays, J. Yeh, L. M. Bjursten, J. A. Frangos, 2006 COX-2 is necessary for venous ligation-mediated bone adaptation in mice. Bone, 38(1):93–104.  10.1016/j.bone.2005.07.006 PubMedCrossRefGoogle Scholar
  99. 99.
    Stoltz J. F., D. Bensoussan, V. Decot, P. Netter, A. Ciree, P. Gillet, 2006 Cell and tissue engineering and clinical applications: An overview. Bio-Medical Materials and Engineering, 16(4):S3–S18PubMedGoogle Scholar
  100. 100.
    Tate M. L. K., 2003 "Whither flows the fluid in bone?" An osteocyte's perspective. Journal of Biomechanics, 36(10):1409–1424.  10.1016/S0021-9290(03)00123-4 CrossRefGoogle Scholar
  101. 101.
    Tate M. L. K., U. Knothe, 2000 An ex vivo model to study transport processes and fluid flow in loaded bone. Journal of Biomechanics, 33(2):247–254.  10.1016/S0021-9290(99)00143-8 CrossRefGoogle Scholar
  102. 102.
    Tate M. L. K., P. Niederer, U. Knothe, 1998 In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. Bone, 22(2):107–117.  10.1016/S8756-3282(97)00234-2 CrossRefGoogle Scholar
  103. 103.
    Tavassoli M., 1976 Ultrastructural development of bone marrow adipose cell. Acta Anat (Basel), 94(1):65–77Google Scholar
  104. 104.
    Tavassoli, M., and J. M. Yoffey. Bone Marrow, Structure and Function. New York: A.R. Liss, pp. xii, 300, 1983.Google Scholar
  105. 105.
    Tenenbaum H. C., Cellular Origins and Theories of Differentiation of Bone-Forming Cells, in In Bone: The Osteoblast and Osteocyte, B.K. Hall, Editor. 1992, CRC Press: Boca Raton, FL. p. 41–69Google Scholar
  106. 106.
    Tettelbaum S. L., M. M. Tondravi F. P. Ross, Osteoclast Biology, in Osteoporosis, S.E. Papapoulos, Editor. 1996, Academic Press: San Diego, CA. p. 61–71Google Scholar
  107. 107.
    Thomas, I. H., P. J. Gregg, and D.N. Walder. Intra-osseous phlebography and intra-medullary pressure in the rabbit femur. J. Bone Joint Surg. Br. 64(2):239–242, 1982Google Scholar
  108. 108.
    Tondevold E., J. Eriksen, E. Jansen, 1979 Observations on Long-Bone Medullary Pressure in Relation to Mean Arterial Blood-Pressure in the Anesthetized Dog. Acta Orthopaedica Scandinavica, 50(5):527–531PubMedCrossRefGoogle Scholar
  109. 109.
    Travlos G. S., 2006 Normal structure, function, and histology of the bone marrow. Toxicologic Pathology, 34(5):548–565.  10.1080/01926230600939856 PubMedCrossRefGoogle Scholar
  110. 110.
    Turner C. H., V. Anne, R. M. V. Pidaparti, 1997 A uniform strain criterion for trabecular bone adaptation: Do continuum-level strain gradients drive adaptation? Journal of Biomechanics, 30(6):555–563.  10.1016/S0021-9290(97)84505-8 PubMedCrossRefGoogle Scholar
  111. 111.
    Turner C. H., M. R. Forwood, M. W. Otter, 1994 Mechanotransduction in Bone - Do Bone-Cells Act as Sensors of Fluid-Flow. Faseb Journal, 8(11):875–878PubMedGoogle Scholar
  112. 112.
    Turner C. H., A. G. Robling, 2005 Mechanisms by which exercise improves bone strength. Journal of Bone and Mineral Metabolism, 23:16–22PubMedGoogle Scholar
  113. 113.
    Turner C. H., Y. Takano, I. Owan, G. A. C. Murrell, 1996 Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. American Journal of Physiology-Endocrinology and Metabolism, 33(4):E634–E639Google Scholar
  114. 114.
    Van den Dolder J., G. N. Bancroft, V. I. Sikavitsas, P. H. M. Spauwen, J. A. Jansen, A. G. Mikos, 2003 Flow perfusion culture of marrow stromal osteoblasts in titanium fiber mesh. Journal of Biomedical Materials Research Part A, 64A(2):235–241.  10.1002/jbm.a.10365 PubMedCrossRefGoogle Scholar
  115. 115.
    Verma S., J. H. Rajaratnam, J. Denton, J. A. Hoyland, R. J. Byers, 2002 Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol, 55(9):693–8.  10.1136/jcp.55.9.693 PubMedCrossRefGoogle Scholar
  116. 116.
    Weinbaum S., S. C. Cowin, Y. Zeng, 1994 A Model for the Excitation of Osteocytes by Mechanical Loading-Induced Bone Fluid Shear Stresses. Journal of Biomechanics, 27(3):339–360.  10.1016/0021-9290(94)90010-8 PubMedCrossRefGoogle Scholar
  117. 117.
    Weiss L., 1976 Hematopoietic Microenvironment of Bone-Marrow - Ultrastructural-Study of Stroma in Rats. Anatomical Record, 186(2):161–184.  10.1002/ar.1091860204 PubMedCrossRefGoogle Scholar
  118. 118.
    Weiss, L. P., G. B. Wislocki, 1956 Seasonal Variations in Hematopoiesis in the Dermal Bones of the 9-Banded Armadillo. Anatomical Record, 126(2): p. 143-&. doi: 10.1002/ar.1091260203 PubMedCrossRefGoogle Scholar
  119. 119.
    Welch R. D., C. E. Johnston, M. J. Waldron, B. Poteet, 1993 Bone Changes Associated with Intraosseous Hypertension in the Caprine Tibia. Journal of Bone and Joint Surgery-American Volume, 75A(1):53–60Google Scholar
  120. 120.
    White D. R., H. Q. Woodard, S. M. Hammond, 1987 Average Soft-Tissue and Bone Models for Use in Radiation-Dosimetry. British Journal of Radiology, 60(717):907–913PubMedCrossRefGoogle Scholar
  121. 121.
    Wilkes C. H., M. B. Visscher, 1975 Some Physiological Aspects of Bone-Marrow Pressure. Journal of Bone and Joint Surgery-American Volume, A 57(1):49–57Google Scholar
  122. 122.
    Zerwekh J. E., L. A. Ruml, F. Gottschalk, C. Y. C. Pak, 1998 The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. Journal of Bone and Mineral Research, 13(10):1594–1601.  10.1359/jbmr.1998.13.10.1594 PubMedCrossRefGoogle Scholar
  123. 123.
    Zhang P., M. Su, Y. L. Liu, A. Hsu, H. Yokota, 2007 Knee loading dynamically alters intramedullary pressure in mouse femora. Bone, 40(2):538–543.  10.1016/j.bone.2006.09.018 PubMedCrossRefGoogle Scholar
  124. 124.
    Zhang, P., M. Su, S. M. Tanaka, and H. Yokota. Knee loading stimulates cortical bone formation in murine femurs. BMC Musculoskelet. Disord. 7, 2006.Google Scholar
  125. 125.
    Zhang P., S. M. Tanaka, H. Jiang, M. Su, H. Yokota, 2005 Loading frequency-dependent enhancement of bone formation in mouse tibia with knee-loading modality. Journal of Bone and Mineral Research, 20(9):S134–S135Google Scholar

Copyright information

© Biomedical Engineering Society 2008

Authors and Affiliations

  1. 1.Weldon School of Biomedical EngineeringPurdue UniversityWest LafayetteUSA

Personalised recommendations