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Flow-induced mechanotransduction in skeletal cells

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Abstract

Human body is subject to many and variegated mechanical stimuli, actuated in different ranges of force, frequency, and duration. The process through which cells “feel” forces and convert them into biochemical cascades is called mechanotransduction. In this review, the effects of fluid shear stress on bone cells will be presented. After an introduction to present the major players in bone system, we describe the mechanoreceptors in bone tissue that can feel and process fluid flow. In the second part of the review, we present an overview of the biological processes and biochemical cascades initiated by fluid shear stress in bone cells.

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References

  • Abed E, Labelle D, Martineau C, Loghin A, Moreau R (2009) Expression of transient receptor potential (TRP) channels in human and murine osteoblast-like cells. Mol Membr Biol 26:146–158

    CAS  PubMed  Google Scholar 

  • Alford AI, Jacobs CR, Donahue HJ (2003) Oscillating fluid flow regulates gap junction communication in osteocytic MLO-Y4 cells by an ERK1/2 MAP kinase-dependent mechanism small star, filled. Bone. 33:64–70

    CAS  PubMed  Google Scholar 

  • Arita NA, Pelaez D, Cheung HS (2011) Activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) is needed for the TGFbeta-induced chondrogenic and osteogenic differentiation of mesenchymal stem cells. Biochem Bioph Res Co 405:564–569

    CAS  Google Scholar 

  • Arnsdorf EJ, Tummala P, Jacobs CR (2009b) Non-canonical Wnt signaling and N-cadherin related beta-catenin signaling play a role in mechanically induced osteogenic cell fate. PLoS One 4(4):e5388

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arthur A, Zannettino A, Panagopoulos R, Kobla S, Sims NA, Stylianou C, Matsuo K, Gronthos S (2011) EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation. Bone. 48:533–542

    CAS  PubMed  Google Scholar 

  • Awane M, Andres PG, Li DJ, Reinecker HC (1999) NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 betainduced chemokine promoter activation in intestinal epithelial cells. J Immunol 162(9):5337–5344

    CAS  PubMed  Google Scholar 

  • Bennett BC, Purdy MD, Baker KA, Acharya C, McIntire WE, Stevens RC, Zhang Q, Harris AL, Abagyan R, Yeager M (2016) An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels. Nat Commun 7:8770–8770

    CAS  PubMed  PubMed Central  Google Scholar 

  • Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. NAR. 28:235–242

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bidwell JP, Pavalko FM (2010) The load-bearing mechanosome revisited. Clin Rev Bone Miner Metab 8:213–223

    PubMed  PubMed Central  Google Scholar 

  • Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42(4):606–615

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521

    CAS  PubMed  Google Scholar 

  • Brown DI, Griendling KK (2009) Nox proteins in signal transduction. Free Radic Biol Med 47(9):1239–1253

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burger EH, Klein-Nulend J (1999) Mechanotransduction in bone--role of the lacuno-canalicular network. FASEB J 13(Suppl):S101–S112

    CAS  PubMed  Google Scholar 

  • Cardoso L, Fritton SP, Gailani G, Benalla M, Cowin SC (2013) Advances in assessment of bone porosity, permeability and interstitial fluid flow. J Biomech 46(2):253–265

    PubMed  Google Scholar 

  • Cargnello M, Roux PP (2012) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 76(2):496

    PubMed Central  Google Scholar 

  • Case N, Ma M, Sen B, Xie Z, Gross TS, Rubin J (2008) Beta-catenin levels influence rapid mechanical responses in osteoblasts. J Biol Chem 283:29196–29205

    CAS  PubMed  PubMed Central  Google Scholar 

  • Case N, Rubin J (2010) Beta-catenin--a supporting role in the skeleton. J Cell Biochem 110:545–553

    CAS  PubMed  PubMed Central  Google Scholar 

  • Case N, Sen B, Thomas JA, Styner M, Xie Z, Jacobs CR, Rubin J (2011) Steady and oscillatory fluid flows produce a similar osteogenic phenotype. Calcif Tissue Int 88:189–197

    CAS  PubMed  Google Scholar 

  • Chachisvilis M, Zhang YL, Frangos JA (2006) G protein-coupled receptors sense fluid shear stress in endothelial cells. Proc Natl Acad Sci U S A 103(42):15463–15468

    PubMed  PubMed Central  Google Scholar 

  • Chen JC, Jacobs CR (2013) Mechanically induced osteogenic lineage commitment of stem cells. Stem Cell Res Ther 4(5):107

    PubMed  PubMed Central  Google Scholar 

  • Chesler AT, Szczot M (2018) Portraits of a pressure sensor. eLife. 7:e34396

    PubMed  PubMed Central  Google Scholar 

  • Compagni A, Logan M, Klein R, Adams RH (2003) Control of skeletal patterning by ephrinB1-EphB interactions. Dev Cell 5:217–230

    CAS  PubMed  Google Scholar 

  • Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A (2010) Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 330(6000):55–60

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cowin SC, Cardoso L (2015) Blood and interstitial flow in the hierarchical pore space architecture of bone tissue. J Biomech 48(5):842–854

    PubMed  Google Scholar 

  • Cox CD, Bae C, Ziegler L, Hartley S, Nikolova-Krstevski V, Rohde PR, Ng CA, Sachs F, Gottlieb PA, Martinac B (2016) Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nat Commun 7:10366

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cukierman E, Pankov R, Stevens DR, Yamada KM (2001) Taking cell-matrix adhesions to the third dimension. Science 294(5547):1708–1712

    CAS  PubMed  Google Scholar 

  • Davidson RM, Tatakis DW, Auerbach AL (1990) Multiple forms of mechanosensitive ion channels in osteoblast-like cells. Pflugers Arch 416(6):646–651

    CAS  PubMed  Google Scholar 

  • Dawson CW, Laverick L, Morris MA, Tramoutanis G, Young LS (2008) Epstein-Barr virus-encoded LMP1 regulates epithelial cell motility and invasion via the ERK-MAPK pathway. J Virol 82(7):3654–3664. https://doi.org/10.1128/JVI.01888-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dela Paz NG, Melchior B, Frangos JA (2017) Shear stress induces Gαq/11 activation independently of G protein-coupled receptor activation in endothelial cells. Am J Phys Cell Phys 312(4):C428–C437

    Google Scholar 

  • Delaine-Smith RM, Reilly GC (2012) Mesenchymal stem cell responses to mechanical stimuli. MLTJ. 2(3):169–180

    PubMed  PubMed Central  Google Scholar 

  • Driscoll TP, Cosgrove BD, Heo SJ, Shurden ZE, Mauck RL (2015) Cytoskeletal to nuclear strain transfer regulates YAP signaling in mesenchymal stem cells. Biophys J 108(12):2783–2793. https://doi.org/10.1016/j.bpj.2015.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dos Remedios CG, Chhabra D, Kekic M, Dedova IV, Tsubakihara M, Berry DA, Nosworthy NJ (2003) Actin and actin binding proteins: regulation of cytoskeletal microfilaments. Physiol Rev 83:433–473

    PubMed  Google Scholar 

  • Duncan RL, Turner CH (1995) Mechanotransduction and the functional response of bone to mechanical strain. Calcif Tissue Int 57(5):344–358

    CAS  PubMed  Google Scholar 

  • Federman M, Nichols G Jr (1974) Bone cell cilia: vestigial or functional organelles? Calcif Tissue Res 17:81–85

    CAS  PubMed  Google Scholar 

  • Ferraro JT, Daneshmand M, Bizios R, Rizzo V (2004) Depletion of plasma membrane cholesterol dampens hydrostatic pressure and shear stress-induced mechanotransduction pathways in osteoblast cultures. Am J Phys Cell Phys 286(4):C831–C839

    CAS  Google Scholar 

  • Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature. 463(7280):485–492

    CAS  PubMed  PubMed Central  Google Scholar 

  • Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simões MJ, Cerri PS (2015) Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int:2015, 421746. https://doi.org/10.1155/2015/421746

    Google Scholar 

  • Fritton SP, Weinbaum S (2009) Fluid and solute transport in bone: flow-induced mechanotransduction. Annu Rev Fluid Mech 41:347–374

    PubMed  PubMed Central  Google Scholar 

  • Galea GL, Meakin LB, Sugiyama T, Zebda N, Sunters A, Taipaleenmaki H, Stein GS, van Wijnen AJ, Lanyon LE, Price JS (2013) Estrogen receptor alpha mediates proliferation of osteoblastic cells stimulated by estrogen and mechanical strain, but their acute down-regulation of the Wnt antagonist Sost is mediated by estrogen receptor beta. J Biol Chem 288:9035–9048

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gifre L, Ruiz-Gaspa S, Monegal A, Nomdedeu B, Filella X, Guanabens N, Peris P (2013) Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. Bone. 57:272–276

    CAS  PubMed  Google Scholar 

  • Gillette JM, Nielsen-Preiss SM (2004) The role of annexin 2 in osteoblastic mineralization. J Cell Sci 117(Pt3):441–449

    CAS  PubMed  Google Scholar 

  • Godin LM, Suzuki S, Jacobs CR, Donahue HJ, Donahue SW (2007) Mechanically induced intracellular calcium waves in osteoblasts demonstrate calcium fingerprints in bone cell mechanotransduction. Biomech Model Mechanobiol 6(6):391–398

    PubMed  Google Scholar 

  • Grossmann TN, Yeh JT, Bowman BR, Chu Q, Moellering RE, Verdine GL (2012) Inhibition of oncogenic Wnt signaling through direct targeting of beta-catenin. Proc Natl Acad Sci U S A 109:17942–17947

    CAS  PubMed  PubMed Central  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(6):355–363

    CAS  PubMed  Google Scholar 

  • Haidekker MA, L’Heureux N, Frangos JA (2000) Fluid shear stress increases membrane fluidity in endothelial cells: a study with DCVJ fluorescence. Am J Physiol Heart Circ Physiol 278:H1401–H1406

    CAS  PubMed  Google Scholar 

  • Harrison OJ, Jin X, Hong S, Bahna F, Ahlsen G, Brasch J, Wu Y, Vendome J, Felsovalyi K, Hampton CM, Troyanovsky RB, Ben-Shaul A, Frank J, Troyanovsky SM, Shapiro L, Honig B (2011) The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins. Structure. 19:244–256

    CAS  PubMed  PubMed Central  Google Scholar 

  • Haut Donahue TL, Genetos DC, Jacobs CR, Donahue HJ, Yellowley CE (2004) Annexin V disruption impairs mechanically induced calcium signaling in osteoblastic cells. Bone. 35:656–663

    CAS  PubMed  Google Scholar 

  • Hehlgans S, Haase M, Cordes N (2007) Signalling via integrins: implications for cell survival and anticancer strategies. Biochim Biophys Acta 1775(1):163–180

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Hillsley MV, Frangos JA (1997) Alkaline phosphatase in osteoblasts is down-regulated by pulsatile fluid flow. Calcif Tissue Int 60:48–53

    CAS  PubMed  Google Scholar 

  • Hoey DA, Kelly DJ, Jacobs CR (2011) A role for the primary cilium in paracrine signaling between mechanically stimulated osteocytes and mesenchymal stem cells. Biochem Biophys Res Commun 412(1):182–187

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hoey DA, Tormey S, Ramcharan S, O’Brien FJ, Jacobs CR (2012) Primary cilia-mediated mechanotransduction in human mesenchymal stem cells. Stem Cells 30:2561–2570

    PubMed  PubMed Central  Google Scholar 

  • Horton ER, Humphries JD, James J, Jones MC, Askari JA, Humphries MJ (2016) The integrin adhesome network at a glance. J Cell Sci 129:4159–4163

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang LW, Ren L, Yang PF, Shang P (2015) Response of osteoblasts to the stimulus of fluid flow. Crit Rev Eukaryot Gene Expr 25(2):153–162

    PubMed  Google Scholar 

  • Hung CT, Allen FD, Mansfield KD, Shapiro IM (1997) Extracellular ATP modulates [Ca2+]i in retinoic acid-treated embryonic chondrocytes. Am J Phys 272:C1611–C1617

    CAS  Google Scholar 

  • Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell. 110(6):673–687

    CAS  PubMed  Google Scholar 

  • Ingber DE (1993) Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J Cell Sci 104:613–627

    PubMed  Google Scholar 

  • Ingber DE (2003a) Mechanobiology and diseases of mechanotransduction. Ann Med 35:564–577

    PubMed  Google Scholar 

  • Ingber DE (2003b) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116(Pt7):1157–1173

    CAS  PubMed  Google Scholar 

  • Jacobs CR, Temiyasathit S, Castillo AB (2010) Osteocyte mechanobiology and pericellular mechanics. Annu Rev Biomed Eng 12:369–400. https://doi.org/10.1146/annurev-bioeng-070909-105302

    Article  CAS  PubMed  Google Scholar 

  • Jacobs CR, Yellowley CE, Davis BR, Zhou Z, Cimbala JM, Donahue HJ (1998) Differential effect of steady versus oscillating flow on bone cells. J Biomech 31:969–976

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jahed Z, Shams H, Mehrbod M, Mofrad MR (2014) Mechanotransduction pathways linking the extracellular matrix to the nucleus. Int Rev Cell Mol Biol 310:171–220

    CAS  PubMed  Google Scholar 

  • Jing D, Lu XL, Luo E, Sajda P, Leong PL, Guo XE (2013) Spatiotemporal properties of intracellular calcium signaling in osteocytic and osteoblastic cell networks under fluid flow. Bone. 53:531–540

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson WA (2017) Two views of the same stimulus. Elife. 6:e30191. https://doi.org/10.7554/eLife.30191

    Article  PubMed  PubMed Central  Google Scholar 

  • Kamel MA, Picconi JL, Lara-Castillo N, Johnson ML (2010) Activation of β-catenin signaling in MLO-Y4 osteocytic cells versus 2T3 osteoblastic cells by fluid flow shear stress and PGE2: implications for the study of mechanosensation in bone. Bone. 47(5):872–881

    CAS  PubMed  PubMed Central  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(3):241–251

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Kelly DJ, Jacobs CR (2010) The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells. Birth Defects Res C Embryo Today 90(1):75–85

    CAS  PubMed  Google Scholar 

  • Klein-Nulend J, Bakker AD, Bacabac RG, Vatsa A, Weinbaum S (2013) Mechanosensation and transduction in osteocytes. Bone. 54(2):182–190

    CAS  PubMed  Google Scholar 

  • Knothe Tate ML, Niederer P, Knothe U (1998) In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. Bone. 22:107–117

    CAS  PubMed  Google Scholar 

  • Knothe Tate ML (2001) Mixing mechanisms and net solute transport in bone. Ann Biomed Eng 29:810–816

    CAS  PubMed  Google Scholar 

  • Knothe Tate ML (2003) “Whither flows the fluid in bone?” an osteocyte’s perspective. J Biomech 36(10):1409–1424

    PubMed  Google Scholar 

  • Kuriakose T, Rada B, Watford WT (2014) Tumor progression locus 2-dependent oxidative burst drives phosphorylation of extracellular signalregulated kinase during TLR3 and 9 signaling. J Biol Chem 289(52):36089–36100. https://doi.org/10.1074/jbc.M114.587121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon RY, Temiyasathit S, Tummala P, Quah CC, Jacobs CR (2010) Primary cilium-dependent mechanosensing is mediated by adenylyl cyclase 6 and cyclic AMP in bone cells. FASEB J 24:2859–2868

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Langenhan T, Piao X, Monk KR (2016) Adhesion G protein-coupled receptors in nervous system development and disease. Nat Rev Neurosci 17:550–561. https://doi.org/10.1038/nrn.2016.86

    Article  CAS  PubMed  Google Scholar 

  • Lewis AH, Grandl J (2015) Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension. eLife. 4:e12088

    PubMed  PubMed Central  Google Scholar 

  • Li J, Duncan RL, Burr DB, Turner CH (2002) L-type calcium channels mediate mechanically induced bone formation in vivo. J Bone Miner Res 17(10):1795–1800

    CAS  PubMed  Google Scholar 

  • Little R, Muimo R, Robson L, Harris K, Grabowski PS (2011) The transient receptor potential ion channel TRPV6 is expressed at low levels in osteoblasts and has little role in osteoblast calcium uptake. PLoS One 6(11):e28166

    CAS  PubMed  PubMed Central  Google Scholar 

  • Litzenberger JB, Kim JB, Tummala P, Jacobs CR (2010) Beta1 integrins mediate mechanosensitive signaling pathways in osteocytes. Calcif Tissue Int 86(4):325–332

    CAS  PubMed  PubMed Central  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

    CAS  PubMed  Google Scholar 

  • Liu L, Yuan W, Wang J (2010) Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol 9(6):659–670

    PubMed  Google Scholar 

  • Lofthouse RA, Davis JR, Frondoza CG, Jinnah RH, Hungerford DS, Hare JM (2001) Identification of caveolae and detection of caveolin in normal human osteoblasts. J Bone Joint Surg (Br) 83:124–129

    CAS  Google Scholar 

  • Lombardi ML, Jaalouk DE, Shanahan CM, Burke B, Roux KJ, Lammerding J (2011) The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton. J Biol Chem 286(30):26743–26753

    CAS  PubMed  PubMed Central  Google Scholar 

  • Luo J, Sun P, Siwko S, Liu M, Xiao J (2019) The role of GPCRs in bone diseases and dysfunctions. Bone Res 7:19

    PubMed  PubMed Central  Google Scholar 

  • Lyons JS, Joca HC, Law RA, Williams KM, Kerr JP, Shi G, Khairallah RJ, Martin SS, Konstantopoulos K, Ward CW, Stains JP (2017) Microtubules tune mechanotransduction through NOX2 and TRPV4 to decrease sclerostin abundance in osteocytes. Sci Signal 10:506

    Google Scholar 

  • Machiyama H, Hirata H, Loh XK, Kanchi MM, Fujita H, Tan SH, Kawauchi K, Sawada Y (2014) Displacement of p130Cas from focal adhesions links actomyosin contraction to cell migration. J Cell Sci 127(Pt16):3440–3450

    CAS  PubMed  Google Scholar 

  • Mahalingam B, Van Agthoven JF, Xiong JP, Alonso JL, Adair BD, Rui X, Anand S, Mehrbod M, Mofrad MR, Burger C, Goodman SL, Arnaout MA (2014) Atomic basis for the species-specific inhibition of alpha V integrins by monoclonal antibody 17E6 is revealed by the crystal structure of alpha V beta 3 ectodomain-17E6 Fab complex. J.Biol.Chem. 289:13801–13809

    CAS  PubMed  PubMed Central  Google Scholar 

  • Malone AM, Anderson CT, Tummala P, Kwon RY, Johnston TR, Stearns T, Jacobs CR (2007a) Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc Natl Acad Sci U S A 104(33):13325–13330

    CAS  PubMed  PubMed Central  Google Scholar 

  • Malone AM, Batra NN, Shivaram G, Kwon RY, You L, Kim CH, Rodriguez J, Jair K, Jacobs CR (2007b) The role of actin cytoskeleton in oscillatory fluid flow-induced signaling in MC3T3-E1 osteoblasts. Am J Phys Cell Phys 292(5):C1830–C1836

    CAS  Google Scholar 

  • Maniotis AJ, Chen CS, Ingber DE (1997) Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci U S A 94(3):849–854

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marie PJ, Haÿ E (2013) Cadherins and Wnt signalling: a functional link controlling bone formation. Bonekey Rep 2:330

    PubMed  PubMed Central  Google Scholar 

  • Martin TJ, Allan EH, Ho PW, Gooi JH, Quinn JM, Gillespie MT, Krasnoperov V, Sims NA (2010) Communication between ephrinB2 and EphB4 within the osteoblast lineage. Adv Exp Med Biol 658:51–60

    CAS  PubMed  Google Scholar 

  • Martins RP, Finan JD, Guilak F, Lee DA (2012) Mechanical regulation of nuclear structure and function. Annu Rev Biomed Eng 14:431–455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuo K, Otaki N (2012) Bone cell interactions through Eph/ephrin: bone modeling, remodeling and associated diseases. Cell Adhes Migr 6:148–156

    Google Scholar 

  • McKay MM, Morrison DK (2007) Integrating signals from RTKs to ERK/MAPK. Oncogene. 26(22):3113–3121

    CAS  PubMed  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

    PubMed  Google Scholar 

  • Mirzaali MJ, Schwiedrzik JJ, Thaiwichai S, Best JP, Michler J, Zysset PK, Wolfram U (2016) Mechanical properties of cortical bone and their relationships with age, gender, composition and microindentation properties in the elderly. Bone. 93:196–211

    PubMed  Google Scholar 

  • Myers KA, Rattner JB, Shrive NG, Hart DA (2007) Osteoblast-like cells and fluid flow: cytoskeleton-dependent shear sensitivity. Biochem Biophys Res Commun 364(2):214–219

    CAS  PubMed  Google Scholar 

  • Nagaraja MP, Jo H (2014) The role of mechanical stimulation in recovery of bone loss-high versus low magnitude and frequency of force. Life (Basel) 4(2):117–130. https://doi.org/10.3390/life4020117

    Article  Google Scholar 

  • Nikolopoulos SN, Turner CE (2000) Actopaxin, a new focal adhesion protein that binds paxillin LD motifs and actin and regulates cell adhesion. J Cell Biol 151(7):1435–1448

    CAS  PubMed  PubMed Central  Google Scholar 

  • Norvell SM, Alvarez M, Bidwell JP, Pavalko FM (2004) Fluid shear stress induces beta-catenin signaling in osteoblasts. Calcif Tissue Int 75:396–404

    CAS  PubMed  Google Scholar 

  • Orr AW, Murphy-Ullrich JE (2004) Regulation of endothelial cell function BY FAK and PYK2. Front Biosci 9:1254–1266

    CAS  PubMed  Google Scholar 

  • Pavalko FM, Chen NX, Turner CH, Burr DB, Atkinson S, Hsieh YF, Qiu J, Duncan RL (1998) Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. Am J Phys 275(6Pt1):C1591–C1601

    CAS  Google Scholar 

  • Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ, Mogha A, Ghidinelli M, Feltri ML, Schöneberg T, Piao X, Monk KR (2015) The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211. Neuron. 85:755–769. https://doi.org/10.1016/j.neuron.2014.12.057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piekarski K, Munro M (1977) Transport mechanism operating between blood supply and osteocytes in long bones. Nature. 269(5623):80–82

    CAS  PubMed  Google Scholar 

  • Poole K, Herget R, Lapatsina L, Ngo HD, Lewin GR (2014) Tuning piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat Commun 5:3520

    PubMed  Google Scholar 

  • Raman M, Chen W, Cobb MH (2007) Differential regulation and properties of MAPKs. Oncogene 26:3100–3112

    CAS  PubMed  Google Scholar 

  • Reich KM, Gay CV, Frangos JA (1990) Fluid shear stress as a mediator of osteoblast cyclic adenosine monophosphate production. J Cell Physiol 143:100–104

    CAS  PubMed  Google Scholar 

  • Reilly GC, Haut TR, Yellowley CE, Donahue HJ, Jacobs CR (2003) Fluid flow induced PGE2 release by bone cells is reduced by glycocalyx degradation whereas calcium signals are not. Biorheology. 40(6):591–603

    CAS  PubMed  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 Phys Cell Phys 290:C776–C784

    CAS  Google Scholar 

  • Riehl BD, Lee JS, Ha L, Lim JY (2015) Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors. J R Soc Interface 12(104):20141351. https://doi.org/10.1098/rsif.2014.1351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283:5866–5875

    CAS  PubMed  Google Scholar 

  • Rose AS, Bradley AR, Valasatava Y, Duarte JD, Prlić A, Rose PW (2018) NGL viewer: web-based molecular graphics for large complexes. Bioinformatics. 34(21):3755–3758. https://doi.org/10.1093/bioinformatics/bty419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roskoski R Jr (2012) ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res 66(2):105–143

    CAS  PubMed  Google Scholar 

  • Saito-Diaz K, Chen TW, Wang X, Thorne CA, Wallace HA, Page-McCaw A, Lee E (2013) The way Wnt works: components and mechanism. Growth Factors 31(1):1–31

    CAS  PubMed  Google Scholar 

  • Salter DM, Robb JE, Wright MO (1997) Electrophysiological responses of human bone cells to mechanical stimulation: evidence for specific integrin function in mechanotransduction. J Bone Miner Res 12(7):1133–1141

    CAS  PubMed  Google Scholar 

  • Schlaepfer DD, Hauck CR, Sieg DJ (1999) Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71(3-4):435–478

    CAS  PubMed  Google Scholar 

  • Sezgin E, Levental I, Mayor S, Eggeling C (2017) The mystery of membrane organization: composition, regulation and roles of lipid rafts. Nat Rev Mol Cell Biol 18(6):361–374

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shao Y, Alicknavitch M, Farach-Carson MC (2005) Expression of voltage sensitive calcium channel (VSCC) L-type Cav1.2 (alpha1C) and T-type Cav3.2 (alpha1H) subunits during mouse bone development. Dev Dyn : an official publication of the American Association of Anatomists 234:54–62

    CAS  Google Scholar 

  • Scholz N, Gehring J, Guan C, Ljaschenko D, Fischer R, Lakshmanan V, Kittel RJ, Langenhan T (2015) The adhesion GPCR latrophilin/CIRL shapes mechanosensation. Cell Rep 11:866–874. https://doi.org/10.1016/j.celrep.2015.04.008

    Article  CAS  PubMed  Google Scholar 

  • Siller-Jackson AJ, Burra S, Gu S, Harris SE, Bonewald LF, Sprague E, Jiang JX (2006) The role of α5 integrin as a mechanosensor in the regulation of connexin 43 hemichannel release of prostaglandin in response to mechanical stress. J Bone Miner Res 21(Suppl 1):S72

    Google Scholar 

  • Soattin L, Fiore M, Gavazzo P, Viti F, Facci P, Raiteri R, Difato F, Pusch M, Vassalli M (2016) The biophysics of piezo1 and piezo2 mechanosensitive channels. Biophys Chem 208:26–33

    CAS  PubMed  Google Scholar 

  • Solomon KR, Adolphson LD, Wank DA, McHugh KP, Hauschka PV (2000a) Caveolae in human and murine osteoblasts. J Bone Miner Res 15:2391–2401

    CAS  PubMed  Google Scholar 

  • Solomon KR, Danciu TE, Adolphson LD, Hecht LE, Hauschka PV (2000) Caveolin-enriched membrane signaling complexes in human and murine osteoblasts. J Bone Miner Res 15:2380–2390

    CAS  PubMed  Google Scholar 

  • Srinivasan PP, Parajuli A, Price C, Wang L, Duncan RL, Kirn-Safran CB (2015) Inhibition of T-type voltage sensitive calcium channel reduces load-induced OA in mice and suppresses the catabolic effect of bone mechanical stress on chondrocytes. PLoS One 10(5):e0127290. https://doi.org/10.1371/journal.pone.0127290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stains JP, Civitelli R (2016) Connexins in the skeleton. Semin Cell Dev Biol 50:31–39

    CAS  PubMed  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

    PubMed  Google Scholar 

  • Stoltz JF, Magdalou J, George D, Chen Y, Li Y, De Isla N, He X, Remond Y (2018) Influence of mechanical forces on bone: introduction to mechanobiology and mechanical adaptation concept. J Cell Immunother 4(1):10–12

    Google Scholar 

  • Sugimoto A, Miyazaki A, Kawarabayashi K, Shono M, Akazawa Y, Hasegawa T, Ueda-Yamaguchi K, Kitamura T, Yoshizaki K, Fukumoto S, Iwamoto T (2017) Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells. Sci Rep 7(1):17696

    PubMed  PubMed Central  Google Scholar 

  • Sun W, Chi S, Li Y, Ling S, Tan Y, Xu Y, Jiang F, Li J, Liu C, Zhong G, Cao D, Jin X, Zhao D, Gao X, Liu Z, Xiao B, Li Y (2019) The mechanosensitive Piezo1 channel is required for bone formation. Elife. 8:e47454. https://doi.org/10.7554/eLife.47454

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson WR, Majid AS, Czymmek KJ, Ruff AL, Garcia J, Duncan RL, Farach-Carson MC (2011) Association of the alpha(2)delta(1) subunit with Ca(v)3.2 enhances membrane expression and regulates mechanically induced ATP release in MLO-Y4 osteocytes. J Bone Miner Res 26:2125–2139

    CAS  PubMed  Google Scholar 

  • Thompson WR, Rubin CT, Rubin J (2012) Mechanical regulation of signaling pathways in bone. Gene. 503(2):179–193

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tsimbouri PM, Childs PG, Pemberton GD, Yang J, Jayawarna V, Orapiriyakul W, Burgess K, González-García C, Blackburn G, Thomas D, Vallejo-Giraldo C, Biggs MJP, Curtis ASG, Salmerón-Sánchez M, Reid S, Dalby MJ (2017) Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor. Nat Biomed Eng 1:758–770

    CAS  PubMed  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(6):346–355

    CAS  PubMed  Google Scholar 

  • Turner CH, Robling AG, Duncan RL, Burr DB (2002) Do bone cells behave like a neuronal network? Calcif Tissue Int 70(6):435–442

    CAS  PubMed  Google Scholar 

  • Ueland T, Olarescu NC, Jorgensen AP, Otterdal K, Aukrust P, Godang K, Lekva T, Bollerslev J (2015) Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with growth hormone deficiency in response to growth hormone treatment. J Clin Endocrinol Metab 100:736–743

    CAS  PubMed  Google Scholar 

  • Verbruggen SW, Vaughan TJ, McNamara LM (2014) Fluid flow in the osteocyte mechanical environment: a fluid-structure interaction approach. Biomech Model Mechanobiol 13(1):85–97. https://doi.org/10.1007/s10237-013-0487-y

    Article  PubMed  Google Scholar 

  • Vezeridis PS, Semeins CM, Chen Q, Klein-Nulend J (2006) Osteocytes subjected to pulsating fluid flow regulate osteoblast proliferation and differentiation. Biochem Biophys Res Commun 348(3):1082–1088

    CAS  PubMed  Google Scholar 

  • Volokh KY, Vilnay O, Belsky M (2002) Cell cytoskeleton and tensegrity. Biorheology. 39(1–2):63–67

    PubMed  Google Scholar 

  • Wang L, Cowin SC, Weinbaum S, Fritton SP (2000) Modeling tracer transport in an osteon under cyclic loading. Ann Biomed Eng 28:1200–1209

    CAS  PubMed  Google Scholar 

  • Wang N, Tytell JD, Ingber DE (2009) Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10:75–82

    CAS  PubMed  Google Scholar 

  • Wang W, Liu Y, Liao K (2011) Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility. BMC Cell Biol 12:49

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Jia L, Zheng Y, Li W (2018) Bone remodeling induced by mechanical forces is regulated by miRNAs. Biosci Rep 38(4):BSR20180448. https://doi.org/10.1042/BSR20180448

    Article  PubMed  PubMed Central  Google Scholar 

  • Wehrli FW, Fernández-Seara MA (2005) Nuclear magnetic resonance studies of bone water. Ann Biomed Eng 33(1):79–86

    PubMed  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(1):85–92

    CAS  PubMed  Google Scholar 

  • Willert K, Nusse R (2012) Wnt proteins. Cold Spring Harb Perspect Biol 4(9):a007864

    PubMed  PubMed Central  Google Scholar 

  • Williams JL, Iannotti JP, Ham A, Bleuit J, Chen JH (1994) Effects of fluid shear stress on bone cells. Biorheology. 31:163–170

    CAS  PubMed  Google Scholar 

  • Winograd-Katz SE, Fässler R, Geiger B, Legate KR (2014) The integrin adhesome: from genes and proteins to human disease. Nat Rev Mol Cell Biol 15(4):273–288

    CAS  PubMed  Google Scholar 

  • Wittkowske C, Reilly GC, Lacroix D, Perrault CM (2016) In vitro bone cell models: impact of fluid shear stress on bone formation. Front Bioeng Biotechnol 4:87

    PubMed  PubMed Central  Google Scholar 

  • Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer BS, Guo D, Dallas SL, Maser R, Calvet JP, Bonewald L, Quarles LD (2006) Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem 281(41):30884–30895

    CAS  PubMed  Google Scholar 

  • Yan Z, Wang P, Wu J, Feng X, Cai J, Zhai M, Li J, Liu X, Jiang M, Luo E, Jing D (2018) Fluid shear stress improves morphology, cytoskeleton architecture, viability, and regulates cytokine expression in a time-dependent manner in MLO-Y4 cells. Cell Biol Int 42(10):1410–1422

    CAS  PubMed  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–H1030

    CAS  PubMed  Google Scholar 

  • Yavropoulou MP, Yovos JG (2016) The molecular basis of bone mechanotransduction. J Musculoskelet Neuronal Interact 16(3):221–236

    CAS  PubMed  PubMed Central  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

    CAS  PubMed  Google Scholar 

  • Yourek G, McCormick SM, Mao JJ, Reilly GC (2010) Shear stress induces osteogenic differentiation of human mesenchymal stem cells. Regen Med 5(5):713–724. https://doi.org/10.2217/rme.10.60

    Article  CAS  PubMed  Google Scholar 

  • Zaidel-Bar R, Cohen M, Addadi L, Geiger B (2004) Hierarchical assembly of cell-matrix adhesion complexes. Biochem Soc Trans 32(Pt3):416–420

    CAS  PubMed  Google Scholar 

  • Zhang K, Barragan-Adjemian C, Ye L, Kotha S, Dallas M, Lu Y, Zhao S, Harris M, Harris SE, Feng JQ, Bonewald LF (2006) E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Mol Cell Biol 26:4539–4552

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Q, Zhou H, Chi S, Wang Y, Wang J, Geng J, Wu K, Liu W, Zhang T, Dong MQ, Wang J, Li X, Xiao B (2018) Structure and mechanogating mechanism of the Piezo1 channel. Nature. 554:487–492

    CAS  PubMed  Google Scholar 

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  1. Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” - National Research Council (IGM-CNR), Via Abbiategrasso, 207, 27100, Pavia, Italy

    Roberta Alfieri

  2. Institute of Biophysics - National Research Council (IBF-CNR), Via De Marini, 6, 16149, Genoa, Italy

    Massimo Vassalli & Federica Viti

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Alfieri, R., Vassalli, M. & Viti, F. Flow-induced mechanotransduction in skeletal cells. Biophys Rev 11, 729–743 (2019). https://doi.org/10.1007/s12551-019-00596-1

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