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Calcified Tissue International

, Volume 57, Issue 5, pp 344–358 | Cite as

Mechanotransduction and the functional response of bone to mechanical strain

  • R. L. Duncan
  • C. H. Turner
Laboratory Investigations

Abstract

Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the cell membrane. G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the magnitude, duration, and rate of the applied load. Longer duration, lower amplitude loading has the same effect on bone formation as loads with short duration and high amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.

Key words

Bone density Calcium channels Integrins Osteoporosis Osteoblasts 

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References

  1. 1.
    Roux W (1905) Die Entwicklungsmechanik; ein neuer Zweig der biologischen Wissenschaft, vols I & II. Wilhelm Engelmann, LeipzigGoogle Scholar
  2. 2.
    Meyer GH (1867) Die architektur der spongiosa. Arch Anat Physiol wiss Med 34:615–628Google Scholar
  3. 3.
    Wolff J (1892) Das Gesetz der Transformation der Knochen. Kirschwald.Google Scholar
  4. 4.
    Dibbets JMH (1992) One century of Wolff's law. In: Carlson DS, Goldstein SA (eds) Bone Biodynamics in Orthodontic and Orthopaedic Treatment. Center for Human Growth and Development, University of Michigan Press, Ann Arbor, pp 1–13Google Scholar
  5. 5.
    Thompson DW (1917) On growth and form. Cambridge University Press, LondonGoogle Scholar
  6. 6.
    Frost HM (1964) Laws of bone structure. Charles C. Thomas, Springfield, ILGoogle Scholar
  7. 7.
    Wronski TJ, Morey ER (1983) Effect of spaceflight on periosteal bone formation in rats. Am J Physiol 244:R305-R309Google Scholar
  8. 8.
    Shaw SR, Vailas AC, Grindeland RE, Zernicke RF (1988) Effects of 1 week spaceflight on morphological and mechanical properties of growing bone. Am J Physiol 254:R78-R83Google Scholar
  9. 9.
    Morey ER, Baylink DJ (1978) Inhibition of bone formation during spaceflight. Science 201:1138–1141Google Scholar
  10. 10.
    Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, Novikov VE, Bakulin AV. (1987) Effects of weightlessness on bone mass and osteoclast number in pregnant rats after a five-day spaceflight (COSMOS 1514). Bone 8:95–103Google Scholar
  11. 11.
    Rambaut PC, Goode AW (1985) Skeletal changes during space flight. Lancet 2:1050–1052Google Scholar
  12. 12.
    Russell JE, Simmons DJ (1985) Bone maturation in rats flown on the Spacelab 3 mission. Physiologist 28:S235-S236Google Scholar
  13. 13.
    Turner RT, Bell NH, Duvall P, Bobyn JD, Spector M, Morey-Holton ER, Baylink DJ. (1985) Spaceflight results in formation of defective bone. Proc Soc Exp Biol Med 180:544–549Google Scholar
  14. 14.
    Cann CE, Adachi RR (1983) Bone resorption and mineral excretion in rats during spaceflight. Am J Physiol 244:R327-R331Google Scholar
  15. 15.
    Patterson-Buckendahl PE, Grindeland RE, Martin RB, Cann CE, Arnaud SB (1985) Osteocalcin as an indicator of bone metabolism during spaceflight. Physiologist 28(suppl):S227-S228Google Scholar
  16. 16.
    Bassey EJ, Ramsdale SJ (1994) Increase in femoral bone density in young women following high-impact exercise. Osteoporosis Int 4:72–75Google Scholar
  17. 17.
    Smith EL, Gilligan C (1990) Exercise and bone mass. In: DeLuca HF, Mazess R (eds) Osteoporosis: Physiological Basis, Assessment and Treatment. Elsevier Science, New York pp 285–293Google Scholar
  18. 18.
    Eisman JA, Kelly PJ, Sambrook PN, Pocock NA, Ward JJ, Yeates MG (1990) Physical activity and bone mass. In: DeLuca HF, Mazess R (eds) Osteoporosis: Physiological Basis, Assessment and Treatment. Elsevier Science, New York, pp 277–283Google Scholar
  19. 19.
    Krolner B, Toft B, Nielsen SP, Tondevold E (1983) Physical exercise as prophylaxis against involutional vertebral bone loss: a controlled trial. Clin Sci 64:541–546Google Scholar
  20. 20.
    Simkin A, Ayalon J, Leichter I (1987) Increased trabecular bone density due to bone-loading exercises in post-menopausal osteoporotic women. Calcif Tissue Int 40:59–63Google Scholar
  21. 21.
    Prince RL, Smith M, Dick IM, Price RI, Webb PG, Henderson NK, Harris MM (1991) Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy. N Eng J Med 325:1189–1195Google Scholar
  22. 22.
    Chesnut CH III (1993) Bone mass and exercise. Am J Med 95:34S-36SGoogle Scholar
  23. 23.
    Currey J (1984) The mechanical adaptations of bones. Princeton University PressGoogle Scholar
  24. 24.
    Frost HM (1983) A determinant of bone architecture. The minimum effective strain. Clin Orthop 200:198–225Google Scholar
  25. 25.
    Burr DB, Martin RB (1992) Mechanisms of bone adaptation to the mechanical environment. Triangle: Sandoz J Med Sci 31:59–76Google Scholar
  26. 26.
    Frost HM (1987) Bone “mass” and the “mechanostat”: a proposal. Anat Rec 219:1–9Google Scholar
  27. 27.
    Hart RT, Davy DT (1989) Theories of bone modeling and remodeling. In: Cowin SC (ed) Bone Mechanics. CRC Press, Boca Raton, FL, pp 253–277Google Scholar
  28. 28.
    Beaupre GS, Orr TE, Carter DR (1990) An approach for time-dependent modeling and remodeling-theoretical development. J Orthop Res 8:651–661Google Scholar
  29. 29.
    Frost HM (1990) Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone modeling problem. Anat Rec 226:403–413Google Scholar
  30. 30.
    Frost HM (1990) Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone remodeling problem. Anat Rec 226:414–422Google Scholar
  31. 31.
    Frangos JA, Eskin SG, McIntire LV, Ives CL (1985) Flow effects on prostacyclin production by cultured human endothelial cells. Science 227:1477–1479Google Scholar
  32. 32.
    Kuchan MJ, Frangos JA (1994) Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells. Am J Physiol 266:C628-C636Google Scholar
  33. 33.
    Rubanyi GM, Freay AD, Kauser K, Johns A, Harder DR (1990) Mechanoreception by the endothelium: mediators and mechanisms of pressure-and flow-induced vascular responses. Blood Vessels 27:246–257Google Scholar
  34. 34.
    Nerem RM, Harrison DB, Taylor WR, Alexander RW (1993) Hemodynamics and vascular endothelial biology. J Cardiovascular Pharm 21:S6-S10Google Scholar
  35. 35.
    Howard J, Roberts WM, Hudspeth AJ (1988) Mechanoelectrical transduction by hair cells. Annu Rev Biophys Biophys Chem 17:99–124Google Scholar
  36. 36.
    Stein RB (1974) Peripheral control of movement. Physiol Rev 54:215Google Scholar
  37. 37.
    Lanyon LE, Hampson WGJ, Goodship AE, Shah JS (1975) Bone deformation recorded in vivo from strain gauges attached to the human tibial shaft. Acta Orthop Scand 46:256–268Google Scholar
  38. 38.
    Burr DB, Milgrom C, Fyhrie D, Forwood M, Nyska M, Finestone A, Saiag E, Simkin A (1995) Human in vivo tibial strains during vigorous activity (abstract). Trans Orthop Res Soc 20:202Google Scholar
  39. 39.
    Rubin CT, Lanyon LE (1982) Limb mechanics as a function of speed and gait: a study of functional strains in the radius and tibia of horse and dog. J Exp Biol 101:187–211Google Scholar
  40. 40.
    Bertram JEA, Biewener AA (1988) Bone curvature: sacrificing strength for load predicatability? J Theor Biol 131:75–92Google Scholar
  41. 41.
    Rubin CT, Lanyon LE (1985) Regulation of bone mass by mechanical strain magnitude. Calcif Tissue Int 37:411–417Google Scholar
  42. 42.
    Weinbaum S, Cowin SC, Zeng Y (1994) A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomechanics 27:339–360Google Scholar
  43. 43.
    Biewener AA, Taylor CR (1986) Bone strain: a determinant of gait and speed? J Exp Biol 123:383–400Google Scholar
  44. 44.
    Hert J, Liskova M, Landa J (1971) Reaction of bone to mechanical stimuli. Part I. Continuous and intermittent loading of tibia in rabbit. Folia Morph 17:290–300Google Scholar
  45. 45.
    Lanyon LE, Rubin CT (1984) Static versus dynamic loads as an influence on bone remodeling. J Biomechanics 17:897–906Google Scholar
  46. 46.
    Turner CH, Owan I, Takano, Y (1995) Mechanotrasduction in bone: the role of strain rate. Am J Physiol (in press)Google Scholar
  47. 47.
    Turner CH, Forwood MR (1995) What role does the osteocyte network play in bone adaptation? Bone 16:283–285Google Scholar
  48. 48.
    Gross TS, McLeod KJ, Rubin CT (1994) Validation of surface strain gradients as a potent predictor of skeletal adaptation (abstract). Trans Orthop Res Soc 19:278Google Scholar
  49. 49.
    Otter MW, Shoenung J, Williams WS (1985) Evidence for different sources of stress-generated potentials in wet and dry bone. J Orthop Res 3:321–324Google Scholar
  50. 50.
    Salzstein RA, Pollack SR, Mak AFT, Petrov N (1987) Electromechanical potentials in cortical bone-I. A continuum approach. J Biomechanics 20:261–270Google Scholar
  51. 51.
    Salzstein RA, Pollack SR (1987) Electromechanical potentials in cortical bone-II. Experimental analysis. J Biomechanics 20:271–280Google Scholar
  52. 52.
    Chakkalakal DA (1989) Mechanoelectric transduction in bone. J Mater Res 4:1034–1046Google Scholar
  53. 53.
    Scott GC, Korostoff E (1990) Oscillatory and step response electromechanical phenomena in human and bovine bone. J Biomechanics 23:127–143Google Scholar
  54. 54.
    Otter MW, Palmieri VR, Wu DD, Seiz KG, MacGinitie LA, Cochran GVB (1992) A comparative analysis of streaming potentials in vivo and in vitro. J Orthop Res 10:710–719Google Scholar
  55. 55.
    McLeod KJ, Rubin CT (1992) The effect of low-frequency electrical fields on osteogenesis. J Bone Jt Surg 74A:920–929Google Scholar
  56. 56.
    Duncan RL, Hruska KA (1994) Chronic, intermittent loading alters mechanosensitive channel characteristics in osteoblast-like cells. Am J Physiol 267:F909-F916Google Scholar
  57. 57.
    Rodan GA, Bourret LA, Harvey A, Mensi T (1975) Cyclic AMP and cyclic GMP: mediators of the mechanical effects on bone remodeling. Science 189:467–469Google Scholar
  58. 58.
    Bourret LA, Rodan GA (1976) The role of calcium in the inhibition of cAMP accumulation in epiphyseal cartilage cells exposed to physiological pressure. J Cell Physiol 88:353–362Google Scholar
  59. 59.
    Veldhuijzen JP, Bourret LA, Rodan GA (1979) In vitro studies of the effect of intermittent compressive forces on cartilage cell proliferation. J Cell Physiol 98:299–307Google Scholar
  60. 60.
    van Kampen GPJ, Veldhuijzen JP, Kuijer R, van de Stadt RJ, Schipper CA (1985) Cartilage response to mechanical force in high density chondrocyte cultures. Arthritis Rheum 28:419–424Google Scholar
  61. 61.
    Ozawa H, Imamura K, Abe E, Takahashi N, Hiraide T, Shibasaki Y, Fukuhara T, Suda T (1990) Effect of continuous applied compressive pressure on mouse osteoblast-like cells (MC3T3-E1) in vitro. J Cell Physiol 142:177–185Google Scholar
  62. 62.
    Harell A, Dekel S, Binderman I (1977) Biochemical effect of mechanical stress on cultured bone cells. Calcif Tissue Res 22(suppl):202–209Google Scholar
  63. 63.
    Somjen D, Binderman I, Berger E, Harell A (1980) Bone remodeling induced by physical stress is prostaglandin E2 mediated. Biochim Biophys Acta 627:91–100Google Scholar
  64. 64.
    Binderman I, Shimshoni Z, Somjen D (1984) Biochemical pathways involved in the translation of physical stimulus into biological message. Calcif Tissue Int 36(suppl):582–585Google Scholar
  65. 65.
    Murray DW, Rushton N (1990) The effect of strain on bone cell prostaglandin E2 release: a new experimental method. Calcif Tissue Int 47:35–39Google Scholar
  66. 66.
    Yeh C, Rodan GA (1984) Tensile forces enhance Prostaglandin E synthesis in osteoblasts grown on collagen ribbon. Calcif Tissue Int 36(suppl):S67-S71Google Scholar
  67. 67.
    Jones DB, Nolte H, Scholubbers J-G, Turner E, Veltel D (1991) Biochemical signal transduction of mechanical strain in osteoblast-like cells. Biomaterials 12:101–110Google Scholar
  68. 68.
    Hasegawa S, Sato S, Saito S, Suzuki Y, Brunette DM (1985) Mechanical stretching increases the number of cultured bone cells synthesizing DNA and alters their pattern of protein synthesis. Calcif Tissue Int 37:431–436Google Scholar
  69. 69.
    Sandy JR, Meghji S, Farndale RW, Meikle MC (1989) Dual evaluation of cyclic AMP and inositol phosphates in response to mechanical deformation of murine osteoblasts. Biochim Biophys Acta 1010:265–269Google Scholar
  70. 70.
    Buckley MJ, Banes AJ, Levin LG, Sumpio BE, Sato M, Jordan R, Gilbert J, Link GW, Tran Son Tay R (1988) Osteoblasts increase their rate of division and align in response to cyclic, mechanical tension. Bone Miner 4:225–236Google Scholar
  71. 71.
    Brighton CT, Sennett BJ, Farmer JC, Iannotti JP, Hansen CA, Williams JL, Williamson J (1992) The inositol phosphate pathway as a mediator in the proliferative response of rat calvarial bone cells to cyclical biaxial mechanical strain. J Orthop Res 10:385–393Google Scholar
  72. 72.
    Reich KM, Frangos JA (1991) Effect of flow on prostaglandin E2 and inositol triphosphate levels in osteoblasts. Am J Physiol 261:C428-C432Google Scholar
  73. 73.
    Reich KM, Gay CV, Frangos JA (1990) Fluid shear stress as a mediator of osteoblast cyclic adenosine monophosphate production. J Cell Physiol 143:100–104Google Scholar
  74. 74.
    Reich KM, Frangos JA (1993) Protein kinase C mediates flow-induced prostaglandin E2 production in osteoblasts. Calcif Tissue Int 52:62–66Google Scholar
  75. 75.
    Ochoa JA, Sanders AP, Heck DA, Hillberry BM (1991) Stiffening of the femoral head due to intertrabecular fluid and intraosseous pressure. J Biomech Eng 113:259–262Google Scholar
  76. 76.
    Carter DR, Wong M (1988) Mechanical stresses and endochondral ossification in the chondroepiphysis. J Orthop Res 6:148–154Google Scholar
  77. 77.
    Carter DR, Wong M (1988) The role of mechanical loading histories in the development of diarthrodial joints. J Orthop Res 6:804–816Google Scholar
  78. 78.
    Burger EH, Klein-Nulend J, Veldhuijzen JP (1991) Modulation of osteogenesis in fetal bone rudiments by mechanical stress in vitro. J Biomech 24(suppl):101–109Google Scholar
  79. 79.
    Turner CH, Forwood MR, Otter MW (1994) Mechanotransduction in bone: Do bone cells act as sensors of fluid flow? FASEB J 8:875–878Google Scholar
  80. 80.
    Rubin CT, Lanyon LE (1984) Regulation of bone formation by applied dynamic loads. J Bone Joint Surg 66A:397–402Google Scholar
  81. 81.
    Turner CH, Forwood MR, Rho J, Yoshikawa T (1994) Mechanical loading thresholds for lamellar and woven bone formation. J Bone Min Res 9:87–97Google Scholar
  82. 82.
    Roer RD, Dillaman RM (1990) Bone growth and calcium balance during simulated weightlessness in the rat. J Appl Physiol 68:13–20Google Scholar
  83. 83.
    Arnaud SB, Sherrard DJ, Maloney N, Whalen RT, Fung P (1992) Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system. Aviat Space Environ Med 63:14–20Google Scholar
  84. 84.
    Dillaman RM, Roer RD, Gay DM (1991) Fluid movement in bone: theoretical and empirical. J Biomech 24(suppl 1):163–177Google Scholar
  85. 85.
    Martin RB, Burr DB (1982) A hypothetical mechanism for the stimulation of osteonal remodelling by fatigue damage. J Biomech 15:137–139Google Scholar
  86. 86.
    Prendergast PJ, Taylor D (1994) Prediction of bone adaptation using damage accumulation. J. Biomech 27:1067–1076Google Scholar
  87. 87.
    Carter DR, Caler WE (1985) A cumulative damage model for bone fracture. J Orthop Res 3:84–90Google Scholar
  88. 88.
    Burr DB, Martin RB, Schaffler MB, Radin EL (1985) Bone remodelling in response to in vivo fatigue microdamage. J Biomech 18:189–200Google Scholar
  89. 89.
    Mori S, Burr DB (1993) Increased intracortical remodeling following fatigue damage. Bone 14:103–109Google Scholar
  90. 90.
    Pavalko FM, Otey CA, Simon KO, Burridge K (1991) α-Actinin: a direct link between actin and integrins. Biochem Soc Trans 19:1065–1069Google Scholar
  91. 91.
    Bockholt SM, Burridge K (1993) Cell spreading on extracellular matrix proteins induces tyrosine phosphorylation of tensin. J Biol Chem 268:14565–14567Google Scholar
  92. 92.
    Sims JR, Karp S, Ingber DE (1992) Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape. J Cell Sci 103:1215–1222Google Scholar
  93. 93.
    Ingber D, Karp S, Plopper G, Hansen L, Mooney D (1993) Mechanochemical transduction across extracellular matrix and through the cytoskeleton. In: Frangos JA (ed) Physical Forces and the Mammalian Cell. Academic Press, New York, pp 61–79Google Scholar
  94. 94.
    Ingber DE (1993) Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J Cell Sci 104: 613–627Google Scholar
  95. 95.
    Fuller JB (1975) Synergetics. Macmillan, New YorkGoogle Scholar
  96. 96.
    McClay DR, Ettensohn CA (1987) Cell adhesion in morphogenesis. Ann Rev Cell Biol 3:319–345Google Scholar
  97. 97.
    Ingber DE, Folkman J (1989) Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol 109:317–330Google Scholar
  98. 98.
    Mooney D, Hansen L, Vacanti J, Langer R, Farmer S, Ingber D (1992) Switching from differentiation to growth in hepatocytes: control by extracellular matrix. J Cell Physiol 151:497–505Google Scholar
  99. 99.
    Ben-Ze'ev A, Robinson GS, Bucher NLR, Farmer SR (1988) Cell-cell and cell-matrix interactions differentially regulate the expression of hepatic and cytoskeletal genes in primary cultures of rat hepatocytes. Proc Natl Acad Sci 85:2161–2165Google Scholar
  100. 100.
    Suda T, Takahashi N, Martin TJ (1992) Modulation of osteoclast differentiation. Endocrine Rev 13:66–80Google Scholar
  101. 101.
    Tenenbaum HC (1992) Cellular origins and theories of differentiation of bone-forming cells. In: Hall K (ed) Bone, Vol. 1: The Osteoblast and Osteocyte. Telford Press, Caldwell, NJ, pp 41–69Google Scholar
  102. 102.
    Manduca P, Pistone M, Sanguineti C, Lu K, Stringa E (1993) Modulation of integrins expression during human osteoblast in vitro differentiation. Boll Soc It Biol Sper 69:699–704Google Scholar
  103. 103.
    Vukicevic S, Luyten FP, Kleinman HK, Reddi AH (1990) Differentiation of canalicular cell processes in bone cells by basement membrane matrix components: regulation by discrete domains of laminin. Cell 63:437–445Google Scholar
  104. 104.
    Brown PD, Benya PD (1988) Alterations in chondrocyte cytoskeletal architecture during phenotypic modulation by retinoic acid and dihydrocytochalasin B-induced re-expression. J Cell Biol 106:171–179Google Scholar
  105. 105.
    Benya PD, Brown PD, Padilla SR (1988) Microfilament modification by dihydrocytochalasin B causes retinoic acidmodulated chondrocytes to re-express the differentiated collagen phenotype without a change in shape. J Cell Biol 106:161–170Google Scholar
  106. 106.
    Dartsch PC, Betz E (1989) Response of cultured endothelial cells to mechanical stimulation. Basic Res Cardiol 84:268–281Google Scholar
  107. 107.
    Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25Google Scholar
  108. 108.
    Ruoslahti E (1991) Integrins. J Clin Invest 87:1–5Google Scholar
  109. 109.
    Dedhar S (1989) Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin-1β in human osteosarcoma cells: inhibition of cell proliferation and stimulation of alkaline phosphatase activity. J Cell Physiol 138:291–299Google Scholar
  110. 110.
    Grzesik WJ, Gehron-Robey P (1994) Bone matrix RGD glycoproteins. Immunolocalization and interaction with human primary osteoblastic bone cell in vitro. J Bone Min Res 9:487–496Google Scholar
  111. 111.
    Gronowicz GA, Derome ME (1994) Synthetic peptide containing Arg-Gly-Asp inhibits bone formation and resorption in a mineralizing organ culture system of fetal rat parietal bone. J Bone Min Res 9:193–201Google Scholar
  112. 112.
    Miyauchi A, Alvarez U, Greenfield EM, Teti A, Grano M, Colucci S, Zambonin-Zallone A, Ross FP, Teitelbaum SL, Cheresh D, Hruska KA (1991) Recognition of osteopontin and related peptides by an αvβ3 integrin stimulates immediate cell signals in the osteoclast. J Biol Chem 226:20369–20374Google Scholar
  113. 113.
    Zimolo Z, Wesolowski G, Tanaka H, Hyman JL, Hoyer JR, Rodan GA (1994) Soluble αvβ3-integrin ligands raise [Ca2+]i in rat osteoclasts and mouse-derived osteoclast-like cells. Am J Physiol 266:C376-C381Google Scholar
  114. 114.
    Schwartz MA (1993) Spreading of human endothelial cells on fibronection or vitronectin triggers elevation of intracellular free calcium. J Cell Biol 120:1003–1010Google Scholar
  115. 115.
    McNamee HP, Ingber DE, Schwartz MA (1993) Adhesion of fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown. J Cell Biol 121:673–678Google Scholar
  116. 116.
    Rornberg LJ, Earp HS, Turner CE, Prockop C, Juliano RL (1991) Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of α5β1 integrins. Proc Natl Acad Sci 88:8392–8396Google Scholar
  117. 117.
    Ingber DE, Pritsty D, Frangioni JV, Cragoe Jr, E.J., Lechene C, Schwartz MA (1990) Control of intracellular pH and growth by fibronectin in capillary endothelial cells. J Cell Biol 110: 1803–1811Google Scholar
  118. 118.
    Schwartz MA, Lechene C, Ingber DE (1991) Insoluble fibionectin activates the Na/H antiporter by clustering and immobilizing integrin α5β1, independent of cell shape. Proc Natl Acad Sci 88:7849–7853Google Scholar
  119. 119.
    Schwartz MA, Ingber DE (1994) Integrating with integrins. Mol Biol Cell 5:389–393Google Scholar
  120. 120.
    Davies PF, Robotewskyj A, Griem ML (1994) Quantitative studies of endothelial cell adhesion: directional remodeling of focal adhesion sites in response to flow forces. J Clin Invest 93:2031–2038Google Scholar
  121. 121.
    Wang N, Butler JP, Ingber DE (1993) Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1127Google Scholar
  122. 122.
    Guharay F, Sachis F (1984) Stretch-activated single ion channel current in tissue cultured embryonic chick skeletal muscle. J Physiol 352:685–701Google Scholar
  123. 123.
    Sachs F (1988) Mechanical transduction in biological systems. Crit Rev Biomed Eng 16:141–169Google Scholar
  124. 124.
    Morris CE (1990) Mechanosensitive ion channels. J Membrane Biol 113:93–107Google Scholar
  125. 125.
    Duncan RL, Misler S (1989) Voltage-activated and stretchactivated Ba2+ conducting channels in an osteoblast-like cell line (UMR-106). FEBS Lett 251:17–21Google Scholar
  126. 126.
    Davidson RM, Tatakis DW, Auerbach AL (1990) Multiple forms of mechanosensitive ion channels in osteoblast-like cells. Pflugers Arch 416:646–651Google Scholar
  127. 127.
    Duncan RL, Hruska KA, Misler S (1992) Parathyroid hormone activation of stretch-activated cation channels in osteosarcoma cells (UMR-106.01). FEBS Lett 307:219–223Google Scholar
  128. 128.
    Miller SS, Wolf AM, Arnaud CD (1976) Bone cells in culture: morphologic transformation by hormones. Science 192:1340–1343Google Scholar
  129. 129.
    Egan JJ, Gronowicz G, Rodan GA (1991) Parathyroid hormone promotes the disassembly of cytoskeletal actin and myosin in cultured osteoblastic cells: mediation by cAMP. J Cell Biochem 45:101–111Google Scholar
  130. 130.
    Lomri A, Marie PJ (1988) Effect of parathyroid hormone and forskolin on cytoskeletal protein synthesis in cultured mouse osteoblastic cells. Biochim Biophys Acta 970:333–342Google Scholar
  131. 131.
    Aubin JE, Alders E, Heersche JNM (1983) A primary role for microfilaments, but not microtubules, in hormone-induced cytoplasmic retraction. Exp Cell Res 143:439–450Google Scholar
  132. 132.
    Cantiello HF, Stow JL, Prat AG, Ausiello DA (1991) Actin filaments regulate epithelial Na+ channel activity. Am J Physiol 261:C882-C888Google Scholar
  133. 133.
    Duncan RL, Harter LV, Levin DW, Hruska KA (1992) Regulation of stretch activated cation channel activity via the cytoskeleton and similar to hormonal modulation (abstract). Mol Biol Cell 3:38aGoogle Scholar
  134. 134.
    Olesen S-P, Clapham DE, Davies PF (1988) Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331:168–170Google Scholar
  135. 135.
    Lansman JB, Hallam TJ, Rink TJ (1987) Single stretchactivated ion channels in vascular endothelial cells as mechanotransducers? Nature 325:811–813Google Scholar
  136. 136.
    Davies PF, Dull RO (1993) Hemodynamic forces in relation to mechanosensitive ion channels in endothelial cells. In: Frangos JA (ed) Physical Forces and the Mammalian Cell. Academic Press, New York; pp 125–138Google Scholar
  137. 137.
    Ypey DL, Ravesloot JH, Buisman HP, Nijweide PJ (1988) Valtage-activated ionic channels and conductances in embryonic chick osteoblast cultures. J Membrane Biol 101:141–150Google Scholar
  138. 138.
    Jones DB, Bingmann D (1991) How do osteoblasts respond to mechanical stimulation? Cells Materials 1:329–340Google Scholar
  139. 139.
    Kinzler KW, Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, et al. (1991) Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 251:1366–1370Google Scholar
  140. 140.
    Kuchan MJ, Jo H, Frangos JA (1994) Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells. Am J Physiol 267:C753-C758Google Scholar
  141. 141.
    Harter LV, Hruska KA, Duncan RL (1995) Human osteoblastlike cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. Endocrinology 136:528–535Google Scholar
  142. 142.
    Burger EH, Veldhuijzen JP (1993) Influence of mechanical factors on bone formation, resorption and growth in vitro. In: Hall BK (ed) Bone Vol. 7: Bone Growth—B. CRC Press, Boca Raton, FL, pp 37–56Google Scholar
  143. 143.
    Parfitt AM (1983) The physiologic and clinical significance of bone histomorphometric data. In: Recker RR (ed) Bone Histomorphometry. CRC Press, Boca Raton, FL, pp 143–223Google Scholar
  144. 144.
    Boyde A (1972) Scanning electron microscope studies of bone. In: Bourne BH (ed) The Biochemistry and Physiology of Bone, vol 1. Academic Press, New York, p 259Google Scholar
  145. 145.
    Frost HM (1960) Measurement of osteocytes per unit volume and volume components of osteocytes and canaliculae in man. Henry Ford Hosp Med Bull 8:208Google Scholar
  146. 146.
    Pead MJ, Suswillo R, Skerry TM, Vedi S, Lanyon LE (1988) Increased 3H uridine levels in osteocytes following a single short period of dynamic bone loading in vivo. Calcif Tissue Int 43:92–96Google Scholar
  147. 147.
    Skerry TM, Bitensky L, Chayen J, Lanyon LE (1989) Early strain-related changes in enzyme activity in osteocytes following bone loading in vivo. J Bone Min Res 4:783–788Google Scholar
  148. 148.
    Dodds RA, Ali N, Pead MJ, Lanyon LE (1993) Early loadingrelated changes in the activity of glucose 6-phosphate dehydrogenase and alkaline phosphatase in osteocytes and periosteal osteoblasts in rat fibulae in vivo. J Bone Min Res 8:261–267Google Scholar
  149. 149.
    Doty SB (1981) Morphological evidence of gap junctions between bone cells. Calcif Tissue Int 33:509–512Google Scholar
  150. 150.
    Menton DN, Simmons DJ, Chang SA-L, Orr BY (1984) From bone lining cell to osteocyte—an SEM study. Anat Rec 209:29–39Google Scholar
  151. 151.
    Palumbo C, Palazzini S, Marotti G (1990) Morphological study of intercellular junctions during osteocyte differentiation. Bone 11:401–406Google Scholar
  152. 152.
    Xia S-L, Ferrier J (1992) Propagation of a calcium pulse between osteoblastic cells. Biochem Biophys Res Comm 186: 1212–1219Google Scholar
  153. 153.
    Jones SJ, Gray C, Sakamaki H, Arora M, Boyde A, Gourdie R, Green C (1993) The incidence and size of gap junctions between the bone cells in rat calvaria. Anat Embryol 187:343–352Google Scholar
  154. 154.
    Vandenburgh HH (1992) Mechanical forces and their second messengers in stimulating cell growth in vitro. Am J Physiol 262:R350-R355Google Scholar
  155. 155.
    Watson PA (1991) Function follows form: generation of intracellular signals by cell deformation. FASEB J 5:2013–2019Google Scholar
  156. 156.
    Sandy JR, Farndale RW (1991) Second messengers: regulators of mechanically induced tissue remodelling. Eur J Orthod 13: 271–278Google Scholar
  157. 157.
    Binderman I, Zor U, Kaye AM, Shimshoni Z, Harell A, Somjen D (1988) The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2. Calcif Tissue Int 42:261–266Google Scholar
  158. 158.
    Kennedy MS, Insel PA (1979) Inhibitors of microtubule assembly emhance beta-adrenergic and prostaglandin E1-stimulated cAMP accumulation in S49 lymphoma cells. Mol Pharmacol 16:215–223Google Scholar
  159. 159.
    Insel PA, Koachman AM (1982) Cytochalasin B enhances hormone and cholera toxin-stimulated cyclic AMP accumulation in S49 lymphoma cells. J Biol Chem 257:9717–9723Google Scholar
  160. 160.
    Vadiakas GP, Banes AJ (1992) Verapamil decrease cyclic load-induced calcium incorporation in ROS 17/2.8 osteosarcoma cell cultures. Matrix 12:439–447Google Scholar
  161. 161.
    Lean JM, Jagger CJ, Chambers TJ, Chow JWM (1995) Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation. Am J Physiol 268:E318-E327Google Scholar
  162. 162.
    Hock JM, Centrella M, Canalis E (1988) Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. Endocrinology 122:254–260Google Scholar
  163. 163.
    Mueller K, Cortesi R, Modrowski D, Marie PJ (1994) Stimulation of trabecular bone formation by insulin-like growth factor I in adult ovariectomized rats. Am J Physiol 267:E1-E6Google Scholar
  164. 164.
    Linkhart TA, Mohan S (1989) Parathyroid hormone stimulates release of insulin-like growth factor I (IGF-I) and IGF-II from neonatal mouse calvaria in organ culture. Endocrinology 125: 1484–1491Google Scholar
  165. 165.
    McCarthy TL, Centrella M, Canalis E (1989) Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone. Endocrinology 124:1247–1253Google Scholar
  166. 166.
    Fitzsimmons RJ, Strong DD, Mohan S, Baylink DJ (1992) Low-amplitude, low-frequency electric field-stimulated bone cell proliferation may in part be mediated by increased IGF-II release. J Cell Physiol 150:84–89Google Scholar
  167. 167.
    Rawlinson SCF, 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 Min Res 6:1345–1351Google Scholar
  168. 168.
    Chow JWM, Chambers TJ (1994) Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation. Am J Physiol 267:E287-E292Google Scholar
  169. 169.
    Rawlinson SCF, Mohan S, Baylink DJ, Lanyon LE (1993) Exogenous prostacyclin, but not prostaglandin E2, productiosimilar 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 53:324–329Google Scholar
  170. 170.
    Norrdin RW, Jee WSS, High WB (1990) The role of prostaglandins in bone in vivo. Prostaglandins Leukot Essent Fatty Acids 41:139–149Google Scholar
  171. 171.
    Miller SC, Marks SC Jr (1993) Local stimulation of new bone formation by prostaglandin E1: quantitative histomorphometry and comparison of delivery by minipumps and controlled-release pellets. Bone 14:143–151Google Scholar
  172. 172.
    Yang RS, Liu TK, Lin-Shiau SY (1993) Increased bone growth by local prostaglandin E2 in rats. Calcif Tissue Int 52:57–61Google Scholar
  173. 173.
    Ma YF, Ke HZ, Jee WSS (1994) Prostaglandin E2 adds bone to a cancellous bone site with a closed growth plate and low bone turnover in ovariectomized rats. Bone 15:137–146Google Scholar
  174. 174.
    Jee WSS, Mori S, Li XJ, Chan S (1990)Prostaglandin E2 enhances cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats. Bone 11: 253–266Google Scholar
  175. 175.
    Mori S, Jee WSS, Li XJ, Chan S, Kimmel DB (1990) Effects of prostaglandin E2 on production of new cancellous bone in the axial skeleton of ovariectomized rats. Bone 11:103–113Google Scholar
  176. 176.
    Ke HZ, Li M, Jee WSS (1992) Prostaglandin E2prevents ovariectomy-induced cancellous bone loss in rats. Bone Miner 19:45–62Google Scholar
  177. 177.
    Ke HZ, Jee WSS, Zeng QQ, Li M, Lin BY (1993) Prostaglandin E2 increased rat cortical bone mass when administered immediately following ovariectomy. Bone Miner 21:189–201Google Scholar
  178. 178.
    Li M, Jee WSS, Ke HZ, Liang XG, Lin BY, Ma YF, Setterberg RB (1993) Prostaglandin E2 restores cancellous bone to immobilized limb and adds bone to overloaded limb in right hindlimb immobilization rats. Bone 14:283–288Google Scholar
  179. 179.
    Jee WSS, Akamine T, Ke HZ, Li XJ, Tang LY, Zeng QQ (1992) Prostaglandin E2 prevents disuse-induced cortical bone loss. Bone 13:153–159Google Scholar
  180. 180.
    Hakeda Y, Yoshino T, Natakani Y, Kurihara N, Maeda N, Kumegawa M (1986) Prostaglandin E2 stimulates DNA synthesis by a cyclic AMP-independent pathway in osteoblastic clone MC3T3-E1 cells. J Cell Physiol128:155–161Google Scholar
  181. 181.
    Yamaguchi DT, Green J, Merritt BS, Kleeman CR, Muallem S (1989) Modulation of osteoblast function by prostaglandins. Am J Physiol 257:F755-F761Google Scholar
  182. 182.
    Nagai M (1980) The effects of prostaglandin E2 on DNA and collagen synthesis in osteoblasts in vitro. Calcif Tissue Int 44:411–420Google Scholar
  183. 183.
    Hakeda Y, Nakatani Y, Hiramatsu M,Kurihara N, Tsunoi M, Ikeda E, Kumegawa M (1985) Inductive effects of prostaglandins on alkaline phosphatase in osteoblastic cells, clone MC3T3-E1. J Biochem 97:97–104Google Scholar
  184. 184.
    Hakeda Y, Nakatani Y, Kurihara N, Ikeda E, Maeda N, Kumegawa M (1985) Prostaglandin E2 stimulates collagen and non-collagen protein synthesis and prolyl hydroxylase activity in osteoblastic clone MC3T3-E1 cells. Biochem Biophys Res Comm 126:340–345Google Scholar
  185. 185.
    Gronowicz GA, Fall PM, Raisz LG (1994) Prostaglandin E2 stimulates preosteoblast replication: an autoradiographic study in cultured fetal rat calvariae. Exp Cell Res 212:314–320Google Scholar
  186. 186.
    Scutt A, Bertram P (1995) Bone marrow cells are targets for the anabolic actions of prostaglandin E2 on bone: induction of a transition from nonadherent to adherent osteoblast precursors. J Bone Min Res 10:474–487Google Scholar
  187. 187.
    Hefti E, Trechsel U, Bonjour J-P, Fleisch H, Schenk R (1982) Increase of whole body calcium and skeletal mass in normal and osteoporotic adult rats treated with parathyroid hormone. Clin Sci 62:389–396Google Scholar
  188. 188.
    Tam CS, Heersche JNM, Murray TM, Parsons JA (1982) Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology 110:506–512Google Scholar
  189. 189.
    Gunness-Hey M, Hock JM (1984) Increased trabecular bone mass in rats treated with human synthetic parathyroid hormone. Metab Bone Dis Rel Res 5:177–181Google Scholar
  190. 190.
    Oxlund H, Ejersted C, Andreassen TT, Torring O, Nilsson MH (1993) Parathyroid hormone (1–34) and (1–84) stimulate cortical bone formation both from periosteum and endosteum. Calcif Tissue Int 53:394–399Google Scholar
  191. 191.
    Wronski TJ, Yen C-F (1994) Anabolic effects of parathyroid hormone on cortical bone in ovariectomized rats. Bone 15:51–58Google Scholar
  192. 192.
    Johansson AG, Baylink DJ, af Ekenstam F, Lindh E, Mohan S, Ljunghall S (1994) Circulating levels of insulin-like growth factor-I and-II, and IGF-binding protein-3 in inflammation and after parathyroid hormone infusion. Bone Miner 24:25–31Google Scholar
  193. 193.
    Canalis E, Centrella M, Burch W, McCarthy TL (1989) Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 83:60–65Google Scholar
  194. 194.
    Nishida S, Yamaguchi A, Tanizawa T, Endo N, Mashiba T, Uchiyama Y, Suda T, Yoshiki S, Takahashi HE (1994) Increased bone formation by intermittent parathyroid hormone administration is due to the stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow. Bone 15:717–723Google Scholar
  195. 195.
    Hock JM, Onyia J, Miller B, Hulman J, Herring J, Chandrasekhar S, Harvey AK, Gunness M (1994) Ahabolic PTH targets proliferating cells of the primary spongiosa in young rats, and increases the number differentiating into osteoblasts (abstract). J Bone Miner Res 9:S412Google Scholar
  196. 196.
    El Haj AJ, Minter SL, Rawlinson SCF, Suswillo R, Lanyon LE (1990) Cellular responses to mechanical loading in vitro. J Bone Min Res 5:923–932Google Scholar
  197. 197.
    Goodship AE, Lanyon LE, McFie H (1979) Functional adaptation of bone to increased stress. J Bone Joint Surg 61A:539–546Google Scholar
  198. 198.
    Lanyon LE, Goodship AE, Pye CJ, MacFie JH (1982) Mechanically adaptive bone remodeling. J Biomech 15:141–154Google Scholar
  199. 199.
    Burr DB, Schaffler MB, Yang KH, Lukoschek M, Sivaneri N, Blaha JD, Radin EL (1989) Skeletal change in response to elevated strain environments: Is woven bone a response to elevated strain. Bone 10:223–233Google Scholar
  200. 200.
    Hert J, Liskova M, Landrgot B (1969) Influence of the longterm, continuous bending on the bone. An experimental study on the tibia of a rabbit. Folia Morphol 17:389–399Google Scholar
  201. 201.
    Liskova M, Hert J (1971) Reaction of bone to mechanical factors. Part 2. Periosteal and endosteal reaction of tibial diaphysis in rabbit to intermittent loading. Folia Morphol 19:301–317Google Scholar
  202. 202.
    O'Connor JA, Lanyon LE, MacFie H, (1982) The influence of strain rate on adaptive bone remodelling. J Biomech 15:767–781Google Scholar
  203. 203.
    Churches AE, Howlett CR (1982) Functional adaptation of bone in response to sinusoidally varying controlled compressive loading of the ovine metacarpus. Clin Orthop Rel Res 168:265–280Google Scholar
  204. 204.
    Lindgren U, Mattsson S(1977) The reversibility of disuse osteoporosis: studies of bone density, bone formation, and cell proliferation in bone tissue. Calcif Tissue Res 23:179–184Google Scholar
  205. 205.
    Unthoff HK, Jaworski ZEG (1978) Bone loss in response to long-term immobilisation. J Bone Jt Surg 60B:420–429Google Scholar
  206. 206.
    Jaworski ZFG, Uhthoff HK (1986) Reversibility of nontraumatic disuse osteoporosis during its active phase. Bone 7:431–439Google Scholar
  207. 207.
    Jee WSS, Li XJ (1990) Adaptation of cancellous bone to overloading in the adult rat: a single photon absorptiometry and histomorphometry study. Anat Rec 227:418–426Google Scholar
  208. 208.
    Jee WSS, Li XJ, Schaffler MB (1991) Adaptation of diaphyseal structure with aging and increased mechanical usage in the adult rat: a histomorphometrical and biomechanical study. Anat Rec 230:332–338Google Scholar
  209. 209.
    Chen MM, Jee WSS, Ke HZ, Lin BY, Li QN, Li XJ (1992) Adaptation of cancellous bone to aging and immobilisation in growing rats. Anat Rec 234:317–334Google Scholar
  210. 210.
    Chambers TJ, Evans M, Gardner TN, Turner-Smith A, Chow JWM (1993) Induction of bone formation in rat tail vertebrae by mechanical loading. Bone Miner 20:167–178Google Scholar
  211. 211.
    Chow JWM, Jagger CJ, Chambers TJ (1993) Characterization of osteogenic response to mechanical stimulation in cancellous bone of rat caudal vertebrae. Am J Physiol 265:E340-E347Google Scholar
  212. 212.
    Torrance AG, Mosley JR, Suswillo RFL, Lanyon LE (1994) Noninvasive loading of rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periosteal pressure. Calcif Tissue Int 54:241–247Google Scholar
  213. 213.
    Turner CH, Akhter MP, Raad DM, Kimmel DB, Recker RR (1991) A non-invasive, in vivo model for studying strain adaptive bone modeling. Bone 12:73–79Google Scholar
  214. 214.
    Forwood MR, Turner CH (1994) Response of rat tibiae to incremental loading: a quantum concept for bone formation. Bone 15:603–609Google Scholar
  215. 215.
    Raab-Cullen DM, Akhter MP, Kimmel DB, Recker RR (1993) Bone response to alternate-day mechanical loading of the rat tibia. J Bone Min Res 9:203–211Google Scholar
  216. 216.
    Hert JM, Liskova M, Landa J (1971) Reaction of bone to mechanical stimuli. Part I. Continuous and intermittent loading of tibia in rabbit. Folia Morph 17:290–300Google Scholar
  217. 217.
    Parfitt AM (1979) The quantum concept of bone remodelling and turnover: implications for the pathogenesis of osteoporosis. Calcif Tissue Int 28:1–5Google Scholar
  218. 218.
    Rubin CT, Bain SD, McLeod KJ (1995) Suppression of the osteogenic response in the aging skeleton. Calcif Tissue Int 50:306–313Google Scholar
  219. 219.
    Turner CH, Takano Y, Owan I (1995) Aging changes mechanical loading thresholds for bone formation in rats. J Bone Min Res (in press)Google Scholar
  220. 220.
    Burkhart JM, Jowsey J (1967) Parathyroid and thyroid hormones in the development of immobilization osteoporosis. Endocrinology 81:1053–1062Google Scholar
  221. 221.
    Turner CH (1991) Homeostatic control of bone structure: an application of feedback theory. Bone 12:203–217Google Scholar
  222. 222.
    Braidman IP, Davenport LK, Carter DH, Selby PL, Mawer EB, Freemont AJ (1995) Preliminary in situ identification of estrogen target cells in bone. J Bone Min Res 10:74–80Google Scholar
  223. 223.
    Galileo G (1638) Discorsi e dimostrazioni matematiche, intorno a due nuove scienze attinente alla meccanica e i movimenti locali. Transl. University of Wisconsin Press, Madison WI, pp 1–346Google Scholar
  224. 224.
    Biewener AA (1990) Biomechanics of mammalian terrestrial locomotion. Science 250:1097–1103Google Scholar
  225. 225.
    Carter DR, Wong M, Orr TE (1991) Musculoskeletal ontogeny, phylogeny, and functional adaptation. J Biomech 24: (suppl) 13–18Google Scholar

Copyright information

© Springer-Verlag New York Inc 1995

Authors and Affiliations

  • R. L. Duncan
    • 1
  • C. H. Turner
    • 1
  1. 1.Biomechanics and Biomaterials Research Center and Department of Orthopaedic SurgeryIndiana University Medical CenterIndianapolisUSA

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