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Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress

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Abstract

Mechanical stimuli can improve bone function by promoting the proliferation and differentiation of bone cells and osteoblasts. As precursors of osteoblasts, human mesenchymal stem cells (hMSCs) are sensitive to mechanical stimuli. In recent years, fluid shear stress (FSS) has been widely used as a method of mechanical stimulation in bone tissue engineering to induce the osteogenic differentiation of hMSCs. However, the mechanism of this differentiation is not completely clear. Several signaling pathways are involved in the mechanotransduction of hMSCs responding to FSS, such as MAPK, NO/cGMP/PKG and Ca2+ signaling pathway. Here, we briefly review how hMSCs respond to fluid flow stimuli and focus on the signal molecules involved in this mechanotransduction.

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References

  • Ali MH, Schumacker PT (2002) Endothelial responses to mechanical stress: where is the mechanosensor? Crit Care Med 30: S198–206

    Article  Google Scholar 

  • Al-Jamal R, Harrison DJ (2008) Beta1 integrin in tissue remodelling and repair: from phenomena to concepts. Pharmacol Ther 120: 81–101

    Article  Google Scholar 

  • Alexander LD, Alagarsamy S, Douglas JG (2004) Cyclic stretch-induced cPLA2 mediates ERK 1/2 signaling in rabbit proximal tubule cells. Kidney Int 65: 551–563

    Article  Google Scholar 

  • Arnsdorf EJ, Tummala P, Kwon RY, Jacobs CR (2009) Mechanically induced osteogenic differentiation-the role of RhoA, ROCKII and cytoskeletal dynamics. J Cell Sci 122: 546–553

    Article  Google Scholar 

  • Baba HA, Stypmann J, Grabellus F, Kirchhof P, Sokoll A, Schafers M, Takeda A, Wilhelm MJ, Scheld HH, Takeda N, Breithardt G, Levkau B (2003) Dynamic regulation of MEK/Erks and Akt/GSK-3beta in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism. Cardiovasc Res 59: 390–399

    Article  Google Scholar 

  • Bancroft GN, Sikavitsas VI, van den Dolder J, Sheffield TL, Ambrose CG, Jansen JA, Mikos AG (2002) Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc Natl Acad Sci U S A 99: 12600–12605

    Article  Google Scholar 

  • Bjerre L, Bunger CE, Kassem M, Mygind T (2008) Flow perfusion culture of human mesenchymal stem cells on silicate-substituted tricalcium phosphate scaffolds. Biomaterials 29: 2616–2627

    Article  Google Scholar 

  • Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (1996) TRAF6 is a signal transducer for interleukin-1. Nature 383: 443–446

    Article  Google Scholar 

  • Catelas I, Sese N, Wu BM, Dunn JC, Helgerson S, Tawil B (2006) Human mesenchymal stem cell proliferation and osteogenic differentiation in fibrin gels in vitro. Tissue Eng 12: 2385–2396

    Article  Google Scholar 

  • Chang C, Werb Z (2001) The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol 11: S37–43

    Google Scholar 

  • Charoonpatrapong-Panyayong K, Shah R, Yang J, Alvarez M, Pavalko FM, Gerard-O’Riley R, Robling AG, Templeton E, Bidwell JP (2007) Nmp4/CIZ contributes to fluid shear stress induced MMP-13 gene induction in osteoblasts. J Cell Biochem 102: 1202–1213

    Article  Google Scholar 

  • Chen YJ, Huang CH, Lee IC, Lee YT, Chen MH, Young TH (2008) Effects of cyclic mechanical stretching on the mRNA expression of tendon/ligament-related and osteoblast-specific genes in human mesenchymal stem cells. Connect Tissue Res 49: 7–14

    Article  Google Scholar 

  • Cherian PP, Cheng B, Gu S, Sprague E, Bonewald LF, Jiang JX (2003) Effects of mechanical strain on the function of Gap junctions in osteocytes are mediated through the prostaglandin EP2 receptor. J Biol Chem 278: 43146–43156

    Article  Google Scholar 

  • Coughlin MF, Schmid-Schonbein GW (2004) Pseudopod projection and cell spreading of passive leukocytes in response to fluid shear stress. Biophys J 87: 2035–2042

    Article  Google Scholar 

  • Damoulis PD, Drakos DE, Gagari E, Kaplan DL (2007) Osteogenic differentiation of human mesenchymal bone marrow cells in silk scaffolds is regulated by nitric oxide. Ann NY Acad Sci 1117: 367–376

    Article  Google Scholar 

  • Ducy P, Karsenty G (1995) Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene. Mol Cell Biol 15: 1858–1869

    Google Scholar 

  • Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89: 747–754

    Article  Google Scholar 

  • Duncan RL, Turner CH (1995) Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int 57: 344–358

    Article  Google Scholar 

  • Espanol AJ, Sales ME (2000) Participation of nitric oxide synthase and cyclo-oxygenase in the signal transduction pathway of ileal muscarinic acetylcholine receptors. Pharmacol Res 42: 489–493

    Article  Google Scholar 

  • Fehrenbacher A, Steck E, Rickert M, Roth W, Richter W (2003) Rapid regulation of collagen but not metalloproteinase 1, 3, 13, 14 and tissue inhibitor of metalloproteinase 1, 2, 3 expression in response to mechanical loading of cartilage explants in vitro. Arch Biochem Biophys 410: 39–47

    Article  Google Scholar 

  • Franceschi RT, Xiao G (2003) Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem 88: 446–454

    Article  Google Scholar 

  • Fu H, Doll B, McNelis T, Hollinger JO (2007) Osteoblast differentiation in vitro and in vivo promoted by osterix. J Biomed Mater Res A 83: 770–778

    Google Scholar 

  • Fu Q, Wu C, Shen Y, Zheng S, Chen R (2008) Effect of LIMK2 RNAi on reorganization of the actin cytoskeleton in osteoblasts induced by fluid shear stress. J Biomech 41: 3225–3228

    Article  Google Scholar 

  • Glossop JR, Cartmell SH (2009) Effect of fluid flow-induced shear stress on human mesenchymal stem cells: differential gene expression of IL1B and MAP3K8 in MAPK signaling. Gene Expr Patterns 9: 381–388

    Article  Google Scholar 

  • Goessler UR, Bugert P, Bieback K, Stern-Straeter J, Bran G, Hormann K, Riedel F (2008) Integrin expression in stem cells from bone marrow and adipose tissue during chondrogenic differentiation. Int J Mol Med 21: 271–279

    Google Scholar 

  • Gouverneur M, Spaan JA, Pannekoek H, Fontijn RD, Vink H (2006) Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx. Am J Physiol Heart Circ Physiol 290: H458–462

    Article  Google Scholar 

  • Grellier M, Bareille R, Bourget C, Amedee J (2009) Responsiveness of human bone marrow stromal cells to shear stress. J Tissue Eng Regen Med 3: 302–309

    Article  Google Scholar 

  • Guharay F, Sachs F (1984) Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle. J Physiol 352: 685–701

    Google Scholar 

  • Gurkan UA, Akkus O (2008) The mechanical environment of bone marrow: a review. Ann Biomed Eng 36: 1978–1991

    Article  Google Scholar 

  • Haasper C, Jagodzinski M, Drescher M, Meller R, Wehmeier M, Krettek C, Hesse E (2008) Cyclic strain induces FosB and initiates osteogenic differentiation of mesenchymal cells. Exp Toxicol Pathol 59: 355–363

    Google Scholar 

  • Harada S, Rodan GA (2003) Control of osteoblast function and regulation of bone mass. Nature 423: 349–355

    Article  Google Scholar 

  • Heubach JF, Graf EM, Leutheuser J, Bock M, Balana B, Zahanich I, Christ T, Boxberger S, Wettwer E, Ravens U (2004) Electrophysiological properties of human mesenchymal stem cells. J Physiol 554: 659–672

    Article  Google Scholar 

  • Humphries MJ (2000) Integrin structure. Biochem Soc Trans 28: 311–339

    Article  Google Scholar 

  • Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110: 673–687

    Article  Google Scholar 

  • Iqbal J, Zaidi M (2005) Molecular regulation of mechanotransduction. Biochem Biophys Res Commun 328: 751–755

    Article  Google Scholar 

  • Jaasma MJ, Jackson WM, Tang RY, Keaveny TM (2007) Adaptation of cellular mechanical behavior to mechanical loading for osteoblastic cells. J Biomech 40: 1938–1945

    Article  Google Scholar 

  • Jaasma MJ, O’Brien FJ (2008) Mechanical stimulation of osteoblasts using steady and dynamic fluid flow. Tissue Eng Part A 14: 1213–1223

    Article  Google Scholar 

  • Kamioka H, Yamashiro T (2008) Osteocytes and mechanical stress. Clin Calcium 18: 1287–1293

    Google Scholar 

  • Kamm RD (2002) Cellular fluid mechanics. Annu Rev Fluid Mech 34: 211–232

    Article  MathSciNet  Google Scholar 

  • Kang H, Bayless KJ, Kaunas R (2008) Fluid shear stress modulates endothelial cell invasion into three-dimensional collagen matrices. Am J Physiol Heart Circ Physiol 295: H2087–H2097

    Article  Google Scholar 

  • Kapur S, Baylink DJ, Lau KH (2003) Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 32: 241–251

    Article  Google Scholar 

  • Kasper G, Glaeser JD, Geissler S, Ode A, Tuischer J, Matziolis G, Perka C, Duda GN (2007) Matrix metalloprotease activity is an essential link between mechanical stimulus and mesenchymal stem cell behavior. Stem Cells 25: 1985–1994

    Article  Google Scholar 

  • Kawano S, Shoji S, Ichinose S, Yamagata K, Tagami M, Hiraoka M (2002) Characterization of Ca2+ signaling pathways in human mesenchymal stem cells. Cell Calcium 32: 165–174

    Article  Google Scholar 

  • Kernan M, Cowan D, Zuker C (1994) Genetic dissection of mechanosensory transduction: mechanoreception-defective mutations of Drosophila. Neuron 12: 1195–1206

    Article  Google Scholar 

  • Kim SH, Choi YR, Park MS, Shin JW, Park KD, Kim SJ, Lee JW (2007) ERK 1/2 activation in enhanced osteogenesis of human mesenchymal stem cells in poly (lactic-glycolic acid) by cyclic hydrostatic pressure. J Biomed Mater Res A 80: 826–836

    Google Scholar 

  • Kleiveland CR, Kassem M, Lea T (2008) Human mesenchymal stem cell proliferation is regulated by PGE2 through differential activation of cAMP-dependent protein kinase isoforms. Exp Cell Res 314: 1831–1838

    Article  Google Scholar 

  • Knippenberg M, Helder MN, Doulabi BZ, Semeins CM, Wuisman PI, Klein-Nulend J (2005) Adipose tissue-derived mesenchymal stem cells acquire bone cell-like responsiveness to fluid shear stress on osteogenic stimulation. Tissue Eng 11: 1708–1780

    Article  Google Scholar 

  • Kreke MR, Goldstein AS (2004) Hydrodynamic shear stimulates osteocalcin expression but not proliferation of bone marrow stromal cells. Tissue Eng 10: 780–788

    Article  Google Scholar 

  • Kreke MR, Huckle WR, Goldstein AS (2005) Fluid flow stimulates expression of osteopontin and bone sialoprotein by bone marrow stromal cells in a temporally dependent manner. Bone 36: 1047–5105

    Article  Google Scholar 

  • Lanctot PM, Gage FH, Varki AP (2007) The glycans of stem cells. Curr Opin Chem Biol 11: 373–380

    Article  Google Scholar 

  • Lee DY, Yeh CR, Chang SF, Lee PL, Chien S, Cheng CK, Chiu JJ (2008) Integrin-mediated expression of bone formation-related genes in osteoblast-like cells in response to fluid shear stress: roles of extracellular matrix, Shc, and mitogen-activated protein kinase. J Bone Miner Res 23: 1140–1149

    Article  Google Scholar 

  • Li S, Butler P, Wang Y, Hu Y, Han DC, Usami S, Guan JL, Chien S (2002) The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells. Proc Natl Acad Sci USA 99: 3546–3551

    Article  Google Scholar 

  • Li YJ, Batra NN, You L, Meier SC, Coe IA, Yellowley CE, Jacobs CR (2004) Oscillatory fluid flow affects human marrow stromal cell proliferation and differentiation. J Orthop Res 22: 1283–1289

    Article  Google Scholar 

  • Liu D, Genetos DC, Shao Y, Geist DJ, Li J, Ke HZ, Turner CH, Duncan RL (2008) Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca(2+)- and ATP-dependent in MC3T3-E1 osteoblasts. Bone 42: 644–652

    Article  Google Scholar 

  • Lopez-Quintero SV, Amaya R, Pahakis M, Tarbell JM (2009) The endothelial glycocalyx mediates shear-induced changes in hydraulic conductivity. Am J Physiol Heart Circ Physiol 296: H1451– 1456

    Article  Google Scholar 

  • Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S (1999) Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285: 895–898

    Article  Google Scholar 

  • Maes F, Van Ransbeeck P, Van Oosterwyck H, Verdonck P (2009) Modeling fluid flow through irregular scaffolds for perfusion bioreactors. Biotechnol Bioeng 103: 621–630

    Article  Google Scholar 

  • Marolt D, Augst A, Freed LE, Vepari C, Fajardo R, Patel N, Gray M, Farley M, Kaplan D, Vunjak-Novakovic G (2006) Bone and cartilage tissue constructs grown using human bone marrow stromal cells, silk scaffolds and rotating bioreactors. Biomaterials 27: 6138–6149

    Article  Google Scholar 

  • Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA, Sheth KV, Eid WA, Dowling O, Harris J, Glucksman MJ, Bahabri S, Meyer BF, Desnick RJ (2001) Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nat Genet 28: 261–265

    Article  Google Scholar 

  • Martino MM, Mochizuki M, Rothenfluh DA, Rempel SA, Hubbell JA, Barker TH (2009) Controlling integrin specificity and stem cell differentiation in 2D and 3D environments through regulation of fibronectin domain stability. Biomaterials 30: 1089–1097

    Article  Google Scholar 

  • McAllister TN, Du T, Frangos JA (2000) Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells. Biochem Biophys Res Commun 270: 643–648

    Article  Google Scholar 

  • McGarry JG, Klein-Nulend J, Prendergast PJ (2005) The effect of cytoskeletal disruption on pulsatile fluid flow-induced nitric oxide and prostaglandin E2 release in osteocytes and osteoblasts. Biochem Biophys Res Commun 330: 341–348

    Article  Google Scholar 

  • McIlhenny SE, Hager ES, Grabo DJ, DiMatteo C, Shapiro IM, Tulenko TN, DiMuzio PJ (2010) Linear shear conditioning improves vascular graft retention of adipose-derived stem cells by upregulation of the alpha5beta1 integrin. Tissue Eng Part A 16: 245–255

    Article  Google Scholar 

  • McMahon LA, Campbell VA, Prendergast PJ (2008) Involvement of stretch-activated ion channels in strain-regulated glycosaminoglycan synthesis in mesenchymal stem cell-seeded 3D scaffolds. J Biomech 41: 2055–2059

    Article  Google Scholar 

  • Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, Janeway CA Jr (1998) MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell 2: 253–258

    Article  Google Scholar 

  • Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16: 558–564

    Article  Google Scholar 

  • Nagel T, Resnick N, Dewey CF Jr, Gimbrone MA Jr (1999) Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arterioscler Thromb Vasc Biol 19: 1825–1834

    Google Scholar 

  • Nijenhuis N, Mizuno D, Schmidt CF, Vink H, Spaan JA (2008) Microrheology of hyaluronan solutions: implications for the endothelial glycocalyx. Biomacromolecules 9: 2390–2398

    Article  Google Scholar 

  • Nijenhuis N, Mizuno D, Spaan JA, Schmidt CF (2009) Viscoelastic response of a model endothelial glycocalyx. Phys Biol 6: 25014

    Article  Google Scholar 

  • Ocarino NM, Boeloni JN, Goes AM, Silva JF, Marubayashi U, Serakides R (2008) Osteogenic differentiation of mesenchymal stem cells from osteopenic rats subjected to physical activity with and without nitric oxide synthase inhibition. Nitric Oxide 19: 320–325

    Article  Google Scholar 

  • Orciani M, Trubiani O, Vignini A, Mattioli-Belmonte M, Di Primio R, Salvolini E (2009) Nitric oxide production during the osteogenic differentiation of human periodontal ligament mesenchymal stem cells. Acta Histochem 111: 15–24

    Article  Google Scholar 

  • Pahakis MY, Kosky JR, Dull RO, Tarbell JM (2007) The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress. Biochem Biophys Res Commun 355: 228–233

    Article  Google Scholar 

  • Parikka V, Vaananen A, Risteli J, Salo T, Sorsa T, Vaananen HK, Lehenkari P (2005) Human mesenchymal stem cell derived osteoblasts degrade organic bone matrix in vitro by matrix metalloproteinases. Matrix Biol 24: 438–447

    Article  Google Scholar 

  • Patwari P, Lee RT (2008) Mechanical control of tissue morphogenesis. Circ Res 103: 234–243

    Article  Google Scholar 

  • Pavalko FM, Norvell SM, Burr DB, Turner CH, Duncan RL, Bidwell JP (2003) A model for mechanotransduction in bone cells: the load-bearing mechanosomes. J Cell Biochem 88: 104–112

    Article  Google Scholar 

  • Pead MJ, Lanyon LE (1989) Indomethacin modulation of load-related stimulation of new bone formation in vivo. Calcif Tissue Int 45: 34–40

    Article  Google Scholar 

  • Ponik SM, Pavalko FM (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

    Article  Google Scholar 

  • Rangaswami H, Marathe N, Zhuang S, Chen Y, Yeh JC, Frangos JA, Boss GR, Pilz RB (2009) Type II cGMP-dependent protein kinase mediates osteoblast mechanotransduction. J Biol Chem 284: 14796–14808

    Article  Google Scholar 

  • Riddle RC, Taylor AF, Genetos DC, Donahue HJ (2006) MAP kinase and calcium signaling mediate fluid flow-induced human mesenchymal stem cell proliferation. Am J Physiol Cell Physiol 290: C776–784

    Article  Google Scholar 

  • Robling AG, Burr DB, Turner CH (2001) Skeletal loading in animals. J Musculoskelet Neuronal Interact 1: 249–262

    Google Scholar 

  • Rodriguez C, Pozo M, Nieto E, Fernandez M, Alemany S (2006) TRAF6 and Src kinase activity regulates Cot activation by IL-1. Cell Signal 18: 1376–1385

    Article  Google Scholar 

  • Rodriguez JP, Gonzalez M, Rios S, Cambiazo V (2004) Cytoskeletal organization of human mesenchymal stem cells (MSC) changes during their osteogenic differentiation. J Cell Biochem 93: 721–731

    Article  Google Scholar 

  • Rodriguez JP, Rios S, Fernandez M, Santibanez JF (2004) Differential activation of ERK1,2 MAP kinase signaling pathway in mesenchymal stem cell from control and osteoporotic postmenopausal women. J Cell Biochem 92: 745–754

    Article  Google Scholar 

  • Rubin J, Rubin C, Jacobs CR (2006) Molecular pathways mediating mechanical signaling in bone. Gene 367: 1–16

    Article  Google Scholar 

  • Sachs F (1986) Biophysics of mechanoreception. Membr Biochem 6: 173–195

    Article  MathSciNet  Google Scholar 

  • Sadoshima J, Takahashi T, Jahn L, Izumo S (1992) Roles of mechano-sensitive ion channels, cytoskeleton, and contractile activity in stretch-induced immediate-early gene expression and hypertrophy of cardiac myocytes. Proc Natl Acad Sci USA 89: 9905–9909

    Article  Google Scholar 

  • Salasznyk RM, Klees RF, Hughlock MK, Plopper GE (2004) ERK signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells on collagen I and vitronectin. Cell Commun Adhes 11: 137–153

    Article  Google Scholar 

  • Salasznyk RM, Klees RF, Boskey A, Plopper GE (2007a) Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5. J Cell Biochem 100: 499–514

    Article  Google Scholar 

  • Salasznyk RM, Klees RF, Williams WA, Boskey A, Plopper GE (2007b) Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells. Exp Cell Res 313:22–37

    Article  Google Scholar 

  • Salter DM, Millward-Sadler SJ, Nuki G, Wright MO (2001) Integrininterleukin-4 mechanotransduction pathways in human chondrocytes. Clin Orthop Relat Res 391:S49–S60

    Article  Google Scholar 

  • Scaglione S, Wendt D, Miggino S, Papadimitropoulos A, Fato M, Quarto R, Martin I (2008) Effects of fluid flow and calcium phosphate coating on human bone marrow stromal cells cultured in a defined 2D model system. J Biomed Mater Res A 86: 411–419

    Google Scholar 

  • Schlaepfer DD, Hauck CR, Sieg DJ (1999) Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71: 435–478

    Article  Google Scholar 

  • Scutt A, Bertram P (1999) Basic fibroblast growth factor in the presence of dexamethasone stimulates colony formation, expansion, and osteoblastic differentiation by rat bone marrow stromal cells. Calcif Tissue Int 64: 69–77

    Article  Google Scholar 

  • Sharp LA, Lee YW, Goldstein AS (2009) Effect of low-frequency pulsatile flow on expression of osteoblastic genes by bone marrow stromal cells. Ann Biomed Eng 37: 445–453

    Article  Google Scholar 

  • Shin MK, Kim MK, Bae YS, Jo I, Lee SJ, Chung CP, Park YJ, Min do S (2008) A novel collagen-binding peptide promotes osteogenic differentiation via Ca2+/calmodulin-dependent protein kinase II/ERK/AP-1 signaling pathway in human bone marrow-derived mesenchymal stem cells. Cell Signal 20: 613–624

    Article  Google Scholar 

  • Siddappa R, Martens A, Doorn J, Leusink A, Olivo C, Licht R, van Rijn L, Gaspar C, Fodde R, Janssen F, van Blitterswijk C, de Boer J (2008) cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo. Proc Natl Acad Sci U S A 105: 7281–7286

    Article  Google Scholar 

  • Simmons CA, Matlis S, Thornton AJ, Chen S, Wang CY, Mooney DJ (2003) Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal-regulated kinase (ERK1/2) signaling pathway. J Biomech 36: 1087–1096

    Article  Google Scholar 

  • Sinha S, Yang W (2008) Cellular signaling for activation of Rho GTPase Cdc42. Cell Signal 20: 1927–1934

    Article  Google Scholar 

  • Stamenkovic I (2000) Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol 10: 415–433

    Article  Google Scholar 

  • Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17: 463–516

    Article  Google Scholar 

  • Stiehler M, Bunger C, Baatrup A, Lind M, Kassem M, Mygind T (2009) Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells. J Biomed Mater Res A 89: 96–107

    Google Scholar 

  • Sumpio BE, Yun S, Cordova AC, Haga M, Zhang J, Koh Y, Madri JA (2005) MAPKs (ERK1/2, p38) and AKT can be phosphorylated by shear stress independently of platelet endothelial cell adhesion molecule-1 (CD31) in vascular endothelial cells. J Biol Chem 280: 11185–11191

    Article  Google Scholar 

  • Swarthout JT, D’Alonzo RC, Selvamurugan N, Partridge NC (2002) Parathyroid hormone-dependent signaling pathways regulating genes in bone cells. Gene 282: 1–17

    Google Scholar 

  • Tarbell JM, Pahakis MY (2006) Mechanotransduction and the glycocalyx. J Intern Med 259: 339–350

    Article  Google Scholar 

  • Tarbell JM, Weinbaum S, Kamm RD (2005) Cellular fluid mechanics and mechanotransduction. Ann Biomed Eng 33: 1719–1723

    Article  Google Scholar 

  • Thi MM, Tarbell JM, Weinbaum S, Spray DC (2004) The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: a “bumper-car” model. Proc Natl Acad Sci U S A 101: 16483–16488

    Article  Google Scholar 

  • Titushkin I, Cho M (2007) Modulation of cellular mechanics during osteogenic differentiation of human mesenchymal stem cells. Biophys J 93: 3693–3702

    Article  Google Scholar 

  • Tschantz P, Rutishauser E (1967) The mechanical overloading of living bone: initial plastic deformations and adaptation hypertrophy. Ann Anat Pathol (Paris) 12: 223–248

    Google Scholar 

  • Turner CH, Pavalko FM (1998) Mechanotransduction and functional response of the skeleton to physical stress: the mechanisms and mechanics of bone adaptation. J Orthop Sci 3: 346–355

    Article  Google Scholar 

  • Turner CH, Forwood MR, Rho JY, Yoshikawa T (1994) Mechanical loading thresholds for lamellar and woven bone formation. J Bone Miner Res 9: 87–97

    Article  Google Scholar 

  • Ward DF Jr, Williams WA, Schapiro NE, Weber GL, Christy SR, Salt M, Klees RF, Boskey A, Plopper GE (2007) Focal adhesion kinase signaling controls cyclic tensile strain enhanced collagen I-induced osteogenic differentiation of human mesenchymal stem cells. Mol Cell Biomech 4: 177–188

    Google Scholar 

  • Weinbaum S, Cowin SC, Zeng Y (1994) A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech 27: 339–360

    Article  Google Scholar 

  • Weyts FA, Li YS, van Leeuwen J, Weinans H, Chien S (2002) ERK activation and alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts. J Cell Biochem 87: 85–92

    Article  Google Scholar 

  • Wolff J (1986) The law of bone remodeling. Translation from the original: Das Gesetz der Transformation der knochen, August Hirsch. Springer

  • Xiao ZS, Quarles LD, Chen QQ, Yu YH, Qu XP, Jiang CH, Deng HW, Li YJ, Zhou HH (2001) Effect of asymmetric dimethylarginine on osteoblastic differentiation. Kidney Int 60: 1699–1704

    Article  Google Scholar 

  • Yang J, Cao C, Wang W, Tong X, Shi D, Wu F, Zheng Q, Guo C, Pan Z, Gao C, Wang J (2010) Proliferation and osteogenesis of immortalized bone marrow-derived mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture. J Biomed Mater Res A 92: 817–829

    Google Scholar 

  • Yao Y, Rabodzey A, Dewey CF Jr (2007) Glycocalyx modulates the motility and proliferative response of vascular endothelium to fluid shear stress. Am J Physiol Heart Circ Physiol 293: H1023– 1030

    Article  Google Scholar 

  • Young SR, Gerard-O’Riley R, Kim JB, Pavalko FM (2009) Focal adhesion kinase is important for fluid shear stress induced mechanotransduction in osteoblasts. J Bone Miner Res 24: 411–424

    Article  Google Scholar 

  • Zayzafoon M (2006) Calcium/calmodulin signaling controls osteoblast growth and differentiation. J Cell Biochem 97: 56–70

    Article  Google Scholar 

  • Zayzafoon M, Gathings WE, McDonald JM (2004) Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology 145: 2421–2432

    Article  Google Scholar 

  • Zhang ZY, Teoh SH, Chong WS, Foo TT, Chng YC, Choolani M, Chan J (2009) A biaxial rotating bioreactor for the culture of fetal mesenchymal stem cells for bone tissue engineering. Biomaterials 30: 2694–2704

    Article  Google Scholar 

  • Zhao F, Chella R, Ma T (2007) Effects of shear stress on 3-D human mesenchymal stem cell construct development in a perfusion bioreactor system: experiments and hydrodynamic modeling. Biotechnol Bioeng 96: 584–595

    Article  Google Scholar 

  • Zhao T, Li Y, Dinner AR (2009) How focal adhesion size depends on integrin affinity. Langmuir 25: 1540–1546

    Article  Google Scholar 

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  1. Institute of Cell Biology, College of Life Sciences, Zhejiang University, 310058, Hangzhou, People’s Republic of China

    Liyue Liu, Wenji Yuan & Jinfu Wang

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  1. Liyue Liu
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Liu, L., Yuan, W. & Wang, J. Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol 9, 659–670 (2010). https://doi.org/10.1007/s10237-010-0206-x

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  • DOI: https://doi.org/10.1007/s10237-010-0206-x

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