Mechanotransduction in bone repair and regeneration

FASEB Journal

Volumn 24, Issue 10, 2010, Pages 3625-3632

  Huang, Chenyu ^a,b   Ogawa, Rei ^a  

^a NIPPON MEDICAL SCHOOL   (Japan)

^b Meitan General Hospital   (China)

Author keywords

Bone reparation and reconstruction; Mechanical stimulation; Mechanosensation; Mechanotransductive pathways; Skeletal adaptation

Indexed keywords

BETA CATENIN; CALCIUM ION; INTEGRIN; NITRIC OXIDE; PROSTAGLANDIN; WNT PROTEIN;

BONE REGENERATION; BONE REMODELING; CELL DIFFERENTIATION; CELL PROLIFERATION; DISTRACTION OSTEOGENESIS; FRACTURE HEALING; HUMAN; MECHANOTRANSDUCTION; NONHUMAN; OSTEOBLAST; OSTEOCYTE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

BONE REGENERATION; HUMANS; MECHANOTRANSDUCTION, CELLULAR; OSTEOGENESIS, DISTRACTION;

EID: 77957851833     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.10-157370     Document Type: Review

References (84)

1. Huang, H., Kamm, R. D., and Lee, R. T. (2004) Cell mechanics and mechanotransduction: pathways, probes, and physiology. Am. J. Physiol. Cell Physiol. 287, C1-C11
2. Turner, C. H., and Pavalko, F. M. (1998) Mechanotransduction and functional response of the skeleton to physical stress: the mechanisms and mechanics of bone adaptation. J. Orthop. Sci. 3, 346-355
3. Frost, H. M. (2003) Bone's mechanostat: a 2003 update. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 275, 1081-1101
4. Inoue, M., Tanaka, H., Moriwake, T., Oka, M., Sekiguchi, C., Seino, Y. (2000) Altered biochemical markers of bone turnover in humans during 120 days of bed rest. Bone 26, 281-286 (Pubitemid 30101653)
5. Smith, S. M., Wastney, M. E., O'Brien, K. O., Morukov, B. V., Larina, I. M., Abrams, S. A., Davis-Street, J. E., Oganov, V., and Shackelford, L. C. (2005) Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir space station. J. Bone Miner. Res. 20, 208-218
6. Robling, A. G., Hinant, F. M., Burr, D. B., and Turner, C. H. (2002) Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J. Bone Miner. Res. 17, 1545-1554
7. Saxon, L. K., Robling, A. G., Alam, I., and Turner, C. H. (2005) Mechanosensitivity of the rat skeleton decreases after a long period of loading, but is improved with time off. Bone 36, 454-464
8. Robling, A. G., Hinant, F. M., Burr, D. B., and Turner, C. H. (2002) Shorter, more frequent mechanical loading sessions enhance bone mass. Med. Sci. Sports Exerc. 34, 196-202
9. Turner, C. H., Takano, Y., and Owan, I. (1995) Aging changes mechanical loading thresholds for bone formation in rats. J. Bone Miner. Res. 10, 1544-1549
10. Nichols, D. L., Sanborn, C. F., and Essery, E. V. (2007) Bone density and young athletic women: an update. Sports Med. 37, 1001-1014
11. Seeman, E. (2004) Estrogen, androgen, and the pathogenesis of bone fragility in women and men. Curr. Osteoporos. Rep. 2, 90-96
12. Seeman, E. (2008) Structural basis of growth-related gain and age-related loss of bone strength. Rheumatology (Oxford) 47(Suppl. 4), iv2-iv8
13. Seeman, E., and Delmas, P. D. (2006) Bone quality-the material and structural basis of bone strength and fragility. N. Engl. J. Med. 354, 2250-2261
14. Robling, A. G., Warden, S. J., Shultz, K. L., Beamer, W. G., and Turner, C. H. (2007) Genetic effects on bone mechanotransduction in congenic mice harboring bone size and strength quantitative trait loci. J. Bone Miner. Res. 22, 984-991
15. David, V., Lafage-Proust, M. H., Laroche, N., Christian, A., Ruegsegger, P., and Vico, L. (2006) Two-week longitudinal survey of bone architecture alteration in the hindlimb-unloaded rat model of bone loss: sex differences. Am. J. Physiol. Endocrinol. Metab. 290, E440-E447
16. Seeman, E. (2008) Bone quality: the material and structural basis of bone strength. J. Bone Miner. Metab. 26, 1-8 (Pubitemid 350308006)
17. Saxon, L. K., and Turner, C. H. (2006) Low-dose estrogen treatment suppresses periosteal bone formation in response to mechanical loading. Bone 39, 1261-1267
18. Isaksson, H., Wilson, W., van Donkelaar, C. C., Huiskes, R., and Ito, K. (2006) Comparison of biophysical stiuli for mechano-regulation of tissue differentiation during fracture healing. J. Biomech. 39, 1507-1516
19. Ilizarov, G. A. (1989) The tension-stress effect on the genesis and growth of tissues: part I. The influence of stability of fixation and soft-tissue preservation. Clin. Orthop. Relat. Res. 238, 249-281
20. Ilizarov, G. A. (1989) The tension-stress effect on the genesis and growth of tissues: part II. The influence of the rate and frequency of distraction. Clin. Orthop. Relat. Res. 239, 263-285 (Pubitemid 19060618)
21. Mi, L. Y., Basu, M., Fritton, S. P., and Cowin, S. C. (2005) Analysis of avian bone response to mechanical loading. Part two: development of a computational connected cellular network to study bone intercellular communication. Biomech. Model. Mechanobiol. 4, 132-146
22. Weinbaum, S., Cowin, S. C., and Zeng, Y. (1994) A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J. Biomech. 27, 339-360
23. Santos, A., Bakker, A. D., and Klein-Nulend, J. (2009) The role of osteocytes in bone mechanotransduction. Osteoporos. Int. 20, 1027-1031
24. Tatsumi, S., Ishii, K., Amizuka, N., Li, M., Kobayashi, T., Kohno, K., Ito, M., Takeshita, S., and Ikeda, K. (2007) Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell. Metab. 5, 464-475 (Pubitemid 46825494)
25. Carter, D. R., Beaupre, G. S., Giori, N. J., and Helms, J. A. (1998) Mechanobiology of skeletal regeneration. Clin. Orthop. Relat. Res. 355, S41-S55
26. Claes, L. E., and Heigele, C. A. (1999) Magnitudes of local stress and strain along osseous surfaces predict the course and type of fracture-healing. J. Biomech. 32, 255-266
27. Prendergast, P. J., Huiskes, R., Soballe, K. (1997) Biophysical stimuli on cells during tissue differentiation at implant interfaces. J. Biomech. 30, 539-548
28. Lacroix, D., Prendergast, P. J. (2002) A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J. Biomech. 35, 1163-1171
29. Morgan, E. F., Gleason, R. E., Hayward, L. N., Leong, P. L., and Palomares, K. T. (2008) Mechanotransduction and fracture repair. J. Bone Joint Surg. Am. 90, 25-30
30. Flick, L. M., Weaver, J. M., Ulrich-Vinther, M., Abuzzahab, F., Zhang, X., Dougall, W. C., Anderson, D., O'Keefe, R. J., and Schwarz, E. M. (2003) Effects of receptor activator of NFkappaB (RANK) signaling blockade on fracture healing. J. Orthop. Res. 21, 676-684
31. Kon, T., Cho, T. J., Aizawa, T., Yamazaki, M., Nooh, N., Graves, D., Gerstenfeld, L. C., and Einhorn, T. A. (2001) Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J. Bone Miner. Res. 16, 1004-1014
32. Tong, L., Buchman, S. R., Ignelzi, M. A., Jr., Rhee, S., and Goldstein, S. A. (2003) Focal adhesion kinase expression during mandibular sistraction osteogenesis: evidence for mechanotransduction. Plast. Reconstr. Surg. 111, 211-222
33. Rhee, S. T., El-Bassiony, L., and Buchman, S. R. (2006) Extracellular signal-related kinase and bone morphogenetic protein expression during distraction osteogenesis of the mandible: in vivo evidence of a mechanotransduction mechanism for differentiation and osteogenesis by mesenchymal precursor cells. Plast. Reconstr. Surg. 117, 2243-2249
34. Rhee, S. T., and Buchman, S. R. (2005) Colocalization of c-Src (pp60src) and bone morphogenetic protein 2/4 expression during mandibular distraction osteogenesis: in vivo evidence of their role within an integrin-mediated mechanotransduction pathway. Ann. Plast. Surg. 55, 207-215
35. Lewinson, D., Rachmie, l, A., Rihani-Bisharat, S., Kraiem, Z., Schenzer, P., Korem, S., and Rabinovich, Y. (2003) Stimulation of Fos- and Jun-related genes during distraction osteogenesis. J. Histochem. Cytochem. 51, 1161-1168
36. Kanno, T., Takahashi, T., Ariyoshi, W., Tsujisawa, T., Haga, M., and Nishihara, T. (2005) Tensile mechanical strain up-regulates Runx2 and osteogenic factor expression in human periosteal cells; implications for distraction osteogenesis. J. Oral Maxillofac. Surg. 63, 499-504 (Pubitemid 40409847)
37. Ingber, D.E. (2003) Tensegrity, II. How structural networks influence cellular information processing networks. J. Cell Sci. 116, 1397-1408
38. Ingber, D. E. (2006) Cellular mechanotransduction: putting all the pieces together again. FASEB J. 20, 811-827
39. Myers, K. A., Battner, J. B., Shrive, N. G., and Hart, D. A. (2007) Hydrostatic pressure sensation in cells: integration into the tensegrity model. Biochem. Cell Biol. 85, 543-551
40. Ingber, D. E. (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 59, 575-599
41. Geiger, B., and Bershadsky, A. (2002) Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell 110, 139-142 (Pubitemid 34876542)
42. Ingber, D. E. (2008) Tensegrity-based mechanosensing from macro to micro. Prog. Biophys. Mol. Biol. 97, 163-179
43. Pavalko, F. M., Norvell, S. M., and Burr, D. B. (2003) A model for mechanotransduction in bone cells: the load-bearing mechanosomes. J. Cell. Biochem. 88, 104-112
44. Vezeridis, P. S., Semeins, C. M., Chen, Q., and Klein-Nulend, J. (2006) Osteocytes subjected to pulsating fluid flow regulate osteoblast proliferation and differentiation. Biochem. Biophys. Res. Commun. 348, 1082-1088
45. Cowin, S. C. (2007) The significance of bone microstructure in mechanotransduction. J. Biomech. 40, S105-S109
46. Klein-Nulend, J., van der Plas, A., Semeins, C. M., Ajubi, N. E., Frangos, J. A., Nijweide, P. J., and Burger, E. H. (1995) Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. 9, 441-445
47. Tan, S. D., de Vries, T. J., Kuijpers-Jagtman, A. M., Semeins, C. M., Everts, V., and Klein-Nulend, J. (2007) Osteocytes subjected to fluid flow inhibit osteoclast formation and bone resorption. Bone 41, 745-751
48. Westbroek, I., Ajubi, N. E., Alblas, M. J., Semeins, C. M., Klein-Nulend, J., Burger, E. H., and Nijweide, P. J. (2000) Differential stimulation of prostaglandin G/H synthase-2 in osteocytes and other osteogenic cells by pulsating fluid flow. Biochem. Biophys. Res. Commun. 268, 414-419 (Pubitemid 30119637)
49. Young, S. R., Gerard-O'Riley, R., Kim, J. B., and Pavalko, F. M. (2009) Focal adhesion kinase is important for fluid shear stress-induced mechanotransduction in osteoblasts. J. Bone Miner. Res. 24, 411-424
50. Ponik, S. M., and Pavalko, F. M. (2004) Formation of focal adhesions on fibronectin promotes fluid shear stress induction of COX-2 and PGE2 release in MC3T3-E1 osteoblasts. J. Appl. Physiol. 97, 135-142
51. Pavalko, F. M., Chen, N. X., Turner, C. H., Burr, D. B., Atkinson, S., Hsieh, Y. F., Qiu, J., and Duncan, R. L. (1998) Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. Am. J. Physiol. 275, C1591-C1601
52. Han, Y., Cowin, S. C., Schaffler, M. B., and Weinbaum, S. (2004) Mechanotransduction and strain amplification in osteocyte cell processes. Proc. Natl. Acad. Sci. U. S. A. 101, 16689-16694
53. Mullender, M. G., Huiskes, R. (1997) Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone? Bone 20, 527-532
54. Rezzonico, R., Cayatte, C., Bourget-Ponzio, I., Romey, G., Belhacene, N., Loubat, A., Rocchi, S., Van Obberghen, E., Girault, J. A., Rossi, B., and Schmid-Antomarchi, H. (2003) Focal adhesion kinase pp125FAK interacts with the large conductance calcium-activated hSlo potassium channel in human osteoblasts: potential role in mechanotransduction. J. Bone Miner. Res. 18, 1863-1871
55. El Haj, A. J., Walker, L. M., Preston, M. R., and Publicover, S. J. (1999) Mechanotransduction pathways in bone: calcium fluxes and the role of voltage-operated calcium channels. Med. Biol. Eng. Comput. 37, 403-409
56. Smalt, R., Mitchell, F. T., Howard, R. L., and Chambers, T. J. (1997) Mechanotransduction in bone cells: induction of nitric oxide and prostaglandin synthesis by fluid shear stress, but not by mechanical strain. Adv. Exp. Med. Biol. 433, 311-314 (Pubitemid 28231838)
57. 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
58. Hung, C. T., Allen, F. D., Pollack, S. R., and Brighton, C. T. (1996) Intracellular Ca2+ stores and extracellular Ca2+ are required in the real-time Ca2+ response of bone cells experiencing fluid flow. J. Biomech. 29, 1411-1417
59. 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
60. Chen, N. X., Ryder, K. D., Pavalko, F. M., Turner, C. H., Burr, D. B., Qiu, J., and Duncan, R. L. (2000) Ca(2+) regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts. Am. J. Physiol. Cell Physiol. 278, C989-C997
61. Leucht, P., Kim, J. B., Currey, J. A., Brunski, J., and Helms, J. A. (2007) FAK-Mediated mechanotransduction in skeletal regeneration. PLoS ONE 2, e390
62. Cheng, B., Kato, Y., Zhao, S., Luo, J., Sprague, E., Bonewald, L. F., and Jiang, J. X. (2001) Prostaglandin E2 is essential for gap junction-mediated intercellular communication between osteocyte-like MLO-Y4 cells in response to mechanical strain. Endocrinology 142, 3464-3473
63. Cherian, P. P., Siller-Jackson, A. J., Gu, S., Wang, X., Bonewald, L. F., Sprague, E., and Jiang, J. X. (2005) Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Mol. Biol. Cell 16, 3100-3106
64. Li, J., Burr, D. B., and Turner, C. H. (2002) Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading. Calcif. Tissue Int. 70, 320-329
65. Alam, I., Warden, S. J., Robling, A. G., and Turner, C. H. (2005) Mechanotransduction in bone does not require a functional cyclooxygenease-2 (COX-2) gene. J. Bone Miner. Res. 20, 438-446
66. Forwood, M. R. (1996) Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. J. Bone Miner. Res. 11, 1688-1693
67. Rubin, J., Murphy, T. C., Zhu, L., Roy, E., Nanes, M. S., and Fan, X. (2003) Mechanical strain differentially regulates endothelial nitric-oxide synthase and receptor activator of nuclear kappa B ligand expression via ERK1/2 MAPK. J. Biol. Chem. 278, 34018-34025
68. Turner, C. H., Takano, Y., Owan, I., and Murrell, G. A. (1996) Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. Am. J. Physiol. 270, E634-E639
69. Hens, J. R., Wilson, K. M., Dann, P., Chen, X., Horowitz, M. C., and Wysolmerski, J. J. (2005) TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro. J. Bone Miner. Res. 20, 1103-1113
70. Robinson, J. A., Chatterjee-Kishore, M., Yaworsky, P. J., Cullen, D. M., Zhao, W., Li, C., Kharode, Y., Sauter, L., Babij, P., Brown, E. L., Hill, A. A., Akhter, M. P., Johnson, M. L., Recker, R. R., Komm, B. S., and Bex, F. J. (2006) Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J. Biol. Chem. 281, 31720-31728
71. Sawakami, K., Robling, A. G., Ai, M., Pitner, N. D., Liu, D., Warden, S. J., Li, J., Maye, P., Rowe, D. W., Duncan, R. L., Warman, M. L., and Turner, C. H. (2006) The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J. Biol. Chem. 281, 23698-23711
72. van der Horst, G., van der Werf, S. M., Farih-Sips, H., van Bezooijen, R. L., Lowik, C. W., and Karperien, M. (2005) Downregulation of Wnt signaling by increased expression of Dickkopf-1 and -2 is a prerequisite for late-stage osteoblast differentiation of KS483 cells. J. Bone Miner. Res. 20, 1867-1877 (Pubitemid 41361889)
73. De Boer, J., Siddappa, R., Gaspar, C., van Apeldoorn, A., Fodde, R., and van Blitterswijk, C. (2004) Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells. Bone 34, 818-826 (Pubitemid 38581127)
74. Jansen, J. H., Eijken, M., Jahr, H., Chiba, H., Verhaar, J. A., van Leeuwen, J. P., and Weinans, H. (2010) Stretch-induced inhibition of Wnt/beta-catenin signaling in mineralizing osteoblasts. J. Orthop. Res. 28, 390-396
75. Riddle, R. C., Taylor, A. F., Rogers, J. R., and Donahue, H. J. (2007) ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. J. Bone Miner. Res. 22, 589-600
76. Lau, K. H., Kapur, S., Kesavan, C., and Baylink, D. J. (2006) Up-regulation of the Wnt, estrogen receptor, insulin-like growth factor-I, and bone morphogenetic protein pathways in C57BL/6J osteoblasts as opposed to C3H/HeJ osteoblasts in part contributes to the differential anabolic response to fluid shear. J. Biol. Chem. 281, 9576-9588
77. Zhang, Y. L., Frangos, J. A., and Chachisvilis, M. (2009) Mechanical stimulus alters conformation of type 1 parathyroid hormone receptor in bone cells. Am. J. Physiol. Cell Physiol. 296, C1391-C1399
78. Aguirre, J. I., Plotkin, L. I., Gortazar, A. R., Millan, M. M., O'Brien, C. A,. Manolagas, S. C., and Bellido, T. (2007) A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J. Biol. Chem. 282, 25501-25508
79. Spurney, R. F., Flannery, P. J., Garner, S. C., Athirakul, K., Liu, S., Guilak, F., and Quarles, L. D. (2002) Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts. J. Clin. Invest. 109, 1361-1371
80. Singh, S. P., Chang, E. I., Gossain, A. K., Mehara, B. J., Galiano, R. D., Jensen, J., Longaker, M. T., Gurtner, G. C., and Saadeh, P. B. (2007) Cyclic mechanical strain increases production of regulators of bone healing in cultured murine osteoblasts. J. Am. Coll. Surg. 204, 426-434
81. Baker, A. B., and Sanders, J. E. (2000) Angiogenesis stimulated by mechanical loading. Microvasc. Res. 60, 177-181
82. Bhatt, K. A., Chang, E. I., Warren, S. M., Lin, S. E., Bastidas, N., Ghali, S., Thibboneir, A., Capla, J. M., McCarthy, J. G., and Gurtner, G. C. (2007) Uniaxial mechanical strain: an in vitro correlate to distraction osteogenesis. J. Surg. Res. 143, 329-336
83. Reich, A., Jaffe, N., Tong, A., Lavelin, I., Genina, O., Pines, M., Sklan, D., Nussinovitch, A., and Monsonego-Ornan, E. (2005) Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization. J. Appl. Physiol. 98, 2381-2389 (Pubitemid 40726941)
84. Robling, A. G., and Turner, C. H. Mechanotransduction in bone: genetic effects on mechanosensitivity in mice. (2002) Bone 31, 562-569