Skip to main content
NCBI home page
Tissue Engineering and Regenerative Medicine logoLink to Tissue Engineering and Regenerative Medicine
. 2016 Feb 2;13(1):1–12. doi: 10.1007/s13770-016-9075-0

Signaling of extracellular matrices for tissue regeneration and therapeutics

Ing Loon Sean Chua 1, Hae-Won Kim 2,3,4, Jae Ho Lee 1,2,3,✉
PMCID: PMC6170996  PMID: 30603379

Abstract

Cells receive important regulatory signals from their extracellular matrix (ECM) and the physical property of the ECM regulates important cellular behaviors like cell proliferation, migration and differentiation. A large part of tissue formation and regeneration depends on cellular interaction with its ECM. A comprehensive understanding of the mechanistic biochemical pathway of the ECM components is necessary for the design of a biomaterial scaffold for tissue engineering. Depending on the type of tissue, the ECM requirement might be different and this would influence its downstream intracellular cell signaling. Here, we reviewed the ECM and its signaling pathway by discussing: 1) classification of the ECM into hard, elastic and soft tissue based on its physical properties, 2) proliferation and differentiation control of the ECM, 3) roles of membrane receptor and its intracellular regulation factor, 4) ECM remodeling via inside-out signaling. By providing a comprehensive overview of the ECM’s role in mechanotransduction and the self-regulatory effect of cells back on the ECM, we hope to provide a better insight of the physical and biochemical cues from the ECM. A sound understanding on the in vivo ECM has implication on the choice of materials and surface coating of biomimetic scaffolds used for tissue regeneration and therapeutics in a cell-free scaffold.

Keywords: Extracellular matrix, Signaling, Tissue regeneration, Biomaterials, Tissue engineering

References

  • 1.Suh H. Tissue restoration, tissue engineering and regenerative medicine. Yonsei Med J. 2000;41:681–684. doi: 10.3349/ymj.2000.41.6.681. [DOI] [PubMed] [Google Scholar]
  • 2.Rosso F, Giordano A, Barbarisi M, Barbarisi A. From cell-ECM interactions to tissue engineering. J Cell Physiol. 2004;199:174–180. doi: 10.1002/jcp.10471. [DOI] [PubMed] [Google Scholar]
  • 3.Hynes RO. The extracellular matrix: not just pretty fibrils. Science. 2009;326:1216–1219. doi: 10.1126/science.1176009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Assoian RK, Klein EA. Growth control by intracellular tension and extracellular stiffness. Trends Cell Biol. 2008;18:347–352. doi: 10.1016/j.tcb.2008.05.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Berrier AL, Yamada KM. Cell-matrix adhesion. J Cell Physiol. 2007;213:565–573. doi: 10.1002/jcp.21237. [DOI] [PubMed] [Google Scholar]
  • 6.Giancotti FG, Ruoslahti E. Integrin signaling. Science. 1999;285:1028–1032. doi: 10.1126/science.285.5430.1028. [DOI] [PubMed] [Google Scholar]
  • 7.Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS. Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell. 2009;5:17–26. doi: 10.1016/j.stem.2009.06.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Chen XD. Extracellular matrix provides an optimal niche for the maintenance and propagation of mesenchymal stem cells. Birth Defects Res C Embryo Today. 2010;90:45–54. doi: 10.1002/bdrc.20171. [DOI] [PubMed] [Google Scholar]
  • 9.Titushkin I, Sun S, Shin J, Cho M. Physicochemical control of adult stem cell differentiation: shedding light on potential molecular mechanisms. J Biomed Biotechnol. 2010;2010:743476. doi: 10.1155/2010/743476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126:677–689. doi: 10.1016/j.cell.2006.06.044. [DOI] [PubMed] [Google Scholar]
  • 11.Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, et al. Tissue-engineered lungs for in vivo implantation. Science. 2010;329:538–541. doi: 10.1126/science.1189345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Teixeira AI, Ilkhanizadeh S, Wigenius JA, Duckworth JK, Inganäs O, Hermanson O. The promotion of neuronal maturation on soft substrates. Biomaterials. 2009;30:4567–4572. doi: 10.1016/j.biomaterials.2009.05.013. [DOI] [PubMed] [Google Scholar]
  • 13.Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–221. doi: 10.1038/nm1684. [DOI] [PubMed] [Google Scholar]
  • 14.Even-Ram S, Artym V, Yamada KM. Matrix control of stem cell fate. Cell. 2006;126:645–647. doi: 10.1016/j.cell.2006.08.008. [DOI] [PubMed] [Google Scholar]
  • 15.Mammoto T, Ingber DE. Mechanical control of tissue and organ development. Development. 2010;137:1407–1420. doi: 10.1242/dev.024166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Wells RG. The role of matrix stiffness in regulating cell behavior. Hepatology. 2008;47:1394–1400. doi: 10.1002/hep.22193. [DOI] [PubMed] [Google Scholar]
  • 17.Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123(24):4195–4200. doi: 10.1242/jcs.023820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci. 2008;121(3):255–264. doi: 10.1242/jcs.006064. [DOI] [PubMed] [Google Scholar]
  • 19.Gurtner GC, Callaghan MJ, Longaker MT. Progress and potential for regenerative medicine. Annu Rev Med. 2007;58:299–312. doi: 10.1146/annurev.med.58.082405.095329. [DOI] [PubMed] [Google Scholar]
  • 20.Gieni RS, Hendzel MJ. Mechanotransduction from the ECM to the genome: are the pieces now in place. J Cell Biochem. 2008;104:1964–1987. doi: 10.1002/jcb.21364. [DOI] [PubMed] [Google Scholar]
  • 21.Haque MA, Nagaoka M, Hexig B, Akaike T. Artificial extracellular matrix for embryonic stem cell cultures: a new frontier of nanobiomaterials. Sci Technol Adv Mater. 2010;11:014106. doi: 10.1088/1468-6996/11/1/014106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering. Biomaterials. 2003;24:4353–4364. doi: 10.1016/S0142-9612(03)00339-9. [DOI] [PubMed] [Google Scholar]
  • 23.Dallas SL. Dynamics of bone extracellular matrix assembly and mineralization. J Musculoskelet Neuronal Interact. 2006;6:370–371. [PubMed] [Google Scholar]
  • 24.Termine JD, Belcourt AB, Conn KM, Kleinman HK. Mineral and collagen-binding proteins of fetal calf bone. J Biol Chem. 1981;256:10403–10408. [PubMed] [Google Scholar]
  • 25.Alford AI, Hankenson KD. Matricellular proteins: extracellular modulators of bone development, remodeling, and regeneration. Bone. 2006;38:749–757. doi: 10.1016/j.bone.2005.11.017. [DOI] [PubMed] [Google Scholar]
  • 26.Ducy P. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia. 2011;54:1291–1297. doi: 10.1007/s00125-011-2155-z. [DOI] [PubMed] [Google Scholar]
  • 27.Karsenty G. The genetic transformation of bone biology. Genes Dev. 1999;13:3037–3051. doi: 10.1101/gad.13.23.3037. [DOI] [PubMed] [Google Scholar]
  • 28.Moriwake T, Seino Y. Recent progress in diagnosis and treatment of osteogenesis imperfecta. Acta Paediatr Jpn. 1997;39:521–527. doi: 10.1111/j.1442-200X.1997.tb03631.x. [DOI] [PubMed] [Google Scholar]
  • 29.Waddington RJ, Roberts HC, Sugars RV, Schönherr E. Differential roles for small leucine-rich proteoglycans in bone formation. Eur Cell Mater. 2003;6:12–21. doi: 10.22203/ecm.v006a02. [DOI] [PubMed] [Google Scholar]
  • 30.Fernández-Tresguerres-Hernández-Gil I, Alobera-Gracia MA, del Canto-Pingarrón M, Blanco-Jerez L. Physiological bases of bone regeneration I. Histology and physiology of bone tissue. Med Oral Patol Oral Cir Bucal. 2006;11:E47–E51. [PubMed] [Google Scholar]
  • 31.McKee MD, Pedraza CE, Kaartinen MT. Osteopontin and wound healing in bone. Cells Tissues Organs. 2011;194:313–319. doi: 10.1159/000324244. [DOI] [PubMed] [Google Scholar]
  • 32.McKee MD, Nanci A. Osteopontin and the bone remodeling sequence. Colloidal-gold immunocytochemistry of an interfacial extracellular matrix protein. Ann N Y Acad Sci. 1995;760:177–189. doi: 10.1111/j.1749-6632.1995.tb44629.x. [DOI] [PubMed] [Google Scholar]
  • 33.Hoang QQ, Sicheri F, Howard AJ, Yang DS. Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature. 2003;425:977–980. doi: 10.1038/nature02079. [DOI] [PubMed] [Google Scholar]
  • 34.Zhang J, Tu Q, Chen J. Applications of transgenics in studies of bone sialoprotein. J Cell Physiol. 2009;220:30–34. doi: 10.1002/jcp.21768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Daamen WF, Veerkamp JH, van Hest JC, van Kuppevelt TH. Elastin as a biomaterial for tissue engineering. Biomaterials. 2007;28:4378–4398. doi: 10.1016/j.biomaterials.2007.06.025. [DOI] [PubMed] [Google Scholar]
  • 36.Kjaer M. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev. 2004;84:649–698. doi: 10.1152/physrev.00031.2003. [DOI] [PubMed] [Google Scholar]
  • 37.Barros CS, Franco SJ, Muller U. Extracellular matrix: functions in the nervous system. Cold Spring Harb Perspect Biol. 2011;3:a005108. doi: 10.1101/cshperspect.a005108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Lefcort F, Venstrom K, McDonald JA, Reichardt LF. Regulation of expression of fibronectin and its receptor, alpha 5 beta 1, during development and regeneration of peripheral nerve. Development. 1992;116:767–782. doi: 10.1242/dev.116.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Mahoney MJ, Anseth KS. Three-dimensional growth and function of neural tissue in degradable polyethylene glycol hydrogels. Biomaterials. 2006;27:2265–2274. doi: 10.1016/j.biomaterials.2005.11.007. [DOI] [PubMed] [Google Scholar]
  • 40.Ruoslahti E. Brain extracellular matrix. Glycobiology. 1996;6:489–492. doi: 10.1093/glycob/6.5.489. [DOI] [PubMed] [Google Scholar]
  • 41.Cornbrooks CJ, Carey DJ, McDonald JA, Timpl R, Bunge RP. In vivo and in vitro observations on laminin production by Schwann cells. Proc Natl Acad Sci U S A. 1983;80:3850–3854. doi: 10.1073/pnas.80.12.3850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Chiu AY, Espinosa de los Monteros A, Cole RA, Loera S, de Vellis J. Laminin and s-laminin are produced and released by astrocytes, Schwann cells, and schwannomas in culture. Glia. 1991;4:11–24. doi: 10.1002/glia.440040103. [DOI] [PubMed] [Google Scholar]
  • 43.Horner PJ, Gage FH. Regenerating the damaged central nervous system. Nature. 2000;407:963–970. doi: 10.1038/35039559. [DOI] [PubMed] [Google Scholar]
  • 44.Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453:314–321. doi: 10.1038/nature07039. [DOI] [PubMed] [Google Scholar]
  • 45.Zhao J, Pestell R, Guan JL. Transcriptional activation of cyclin D1 promoter by FAK contributes to cell cycle progression. Mol Biol Cell. 2001;12:4066–4077. doi: 10.1091/mbc.12.12.4066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Schrader J, Gordon-Walker TT, Aucott RL, van Deemter M, Quaas A, Walsh S, et al. Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology. 2011;53:1192–1205. doi: 10.1002/hep.24108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Blau HM, Baltimore D. Differentiation requires continuous regulation. J Cell Biol. 1991;112:781–783. doi: 10.1083/jcb.112.5.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Kulangara K, Yang Y, Yang J, Leong KW. Nanotopography as modulator of human mesenchymal stem cell function. Biomaterials. 2012;33:4998–5003. doi: 10.1016/j.biomaterials.2012.03.053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Tsimbouri P, Gadegaard N, Burgess K, White K, Reynolds P, Herzyk P, et al. Nanotopographical effects on mesenchymal stem cell morphology and phenotype. J Cell Biochem. 2014;115:380–390. doi: 10.1002/jcb.24673. [DOI] [PubMed] [Google Scholar]
  • 50.Lutolf MP, Gilbert PM, Blau HM. Designing materials to direct stem-cell fate. Nature. 2009;462:433–441. doi: 10.1038/nature08602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Ingber DE. Cellular mechanotransduction: putting all the pieces together again. FASEB J. 2006;20:811–827. doi: 10.1096/fj.05-5424rev. [DOI] [PubMed] [Google Scholar]
  • 52.Orr AW, Helmke BP, Blackman BR, Schwartz MA. Mechanisms of mechanotransduction. Dev Cell. 2006;10:11–20. doi: 10.1016/j.devcel.2005.12.006. [DOI] [PubMed] [Google Scholar]
  • 53.Larsen M, Artym VV, Green JA, Yamada KM. The matrix reorganized: extracellular matrix remodeling and integrin signaling. Curr Opin Cell Biol. 2006;18:463–471. doi: 10.1016/j.ceb.2006.08.009. [DOI] [PubMed] [Google Scholar]
  • 54.Vogel WF, Abdulhussein R, Ford CE. Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal. 2006;18:1108–1116. doi: 10.1016/j.cellsig.2006.02.012. [DOI] [PubMed] [Google Scholar]
  • 55.Mecham RP, Hinek A. Non-integrin laminin receptors. In: Ekblom P, Timpl R, editors. The Laminins. New York, USA: Harwood Academic Publishers; 1996. pp. 159–183. [Google Scholar]
  • 56.Streuli CH. Integrins and cell-fate determination. J Cell Sci. 2009;122(2):171–177. doi: 10.1242/jcs.018945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Sottile J, Hocking DC. Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions. Mol Biol Cell. 2002;13:3546–3559. doi: 10.1091/mbc.E02-01-0048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Howe A, Aplin AE, Alahari SK, Juliano RL. Integrin signaling and cell growth control. Curr Opin Cell Biol. 1998;10:220–231. doi: 10.1016/S0955-0674(98)80144-0. [DOI] [PubMed] [Google Scholar]
  • 59.Klees RF, Salasznyk RM, Vandenberg S, Bennett K, Plopper GE. Laminin-5 activates extracellular matrix production and osteogenic gene focusing in human mesenchymal stem cells. Matrix Biol. 2007;26:106–114. doi: 10.1016/j.matbio.2006.10.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Lee DY, Yeh CR, Chang SF, Lee PL, Chien S, Cheng CK, et al. 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. 2008;23:1140–1149. doi: 10.1359/jbmr.080302. [DOI] [PubMed] [Google Scholar]
  • 61.Salasznyk RM, Williams WA, Boskey A, Batorsky A, Plopper GE. Adhesion to vitronectin and collagen I promotes osteogenic differentiation of human mesenchymal stem cells. J Biomed Biotechnol. 2004;2004:24–34. doi: 10.1155/S1110724304306017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Martino MM, Mochizuki M, Rothenfluh DA, Rempel SA, Hubbell JA, Barker TH. Controlling integrin specificity and stem cell differentiation in 2D and 3D environments through regulation of fibronectin domain stability. Biomaterials. 2009;30:1089–1097. doi: 10.1016/j.biomaterials.2008.10.047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Weyts FA, Li YS, van Leeuwen J, Weinans H, Chien S. ERK activation and alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts. J Cell Biochem. 2002;87:85–92. doi: 10.1002/jcb.10278. [DOI] [PubMed] [Google Scholar]
  • 64.Kapur S, Baylink DJ, Lau KH. Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone. 2003;32:241–251. doi: 10.1016/S8756-3282(02)00979-1. [DOI] [PubMed] [Google Scholar]
  • 65.McIlhenny SE, Hager ES, Grabo DJ, DiMatteo C, Shapiro IM, Tulenko TN, et al. Linear shear conditioning improves vascular graft retention of adipose-derived stem cells by upregulation of the alpha5beta1 integrin. Tissue Eng Part A. 2010;16:245–255. doi: 10.1089/ten.tea.2009.0238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Leitinger B. Transmembrane collagen receptors. Annu Rev Cell Dev Biol. 2011;27:265–290. doi: 10.1146/annurev-cellbio-092910-154013. [DOI] [PubMed] [Google Scholar]
  • 67.Fu HL, Valiathan RR, Arkwright R, Sohail A, Mihai C, Kumarasiri M, et al. Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling. J Biol Chem. 2013;288:7430–7437. doi: 10.1074/jbc.R112.444158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Bullard KM, Longaker MT, Lorenz HP. Fetal wound healing: current biology. World J Surg. 2003;27:54–61. doi: 10.1007/s00268-002-6737-2. [DOI] [PubMed] [Google Scholar]
  • 69.Olaso E, Ikeda K, Eng FJ, Xu L, Wang LH, Lin HC, et al. DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest. 2001;108:1369–1378. doi: 10.1172/JCI200112373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Spofford CM, Chilian WM. The elastin-laminin receptor functions as a mechanotransducer in vascular smooth muscle. Am J Physiol Heart Circ Physiol. 2001;280:H1354–H1360. doi: 10.1152/ajpheart.2001.280.3.H1354. [DOI] [PubMed] [Google Scholar]
  • 71.Boudreau NJ, Jones PL. Extracellular matrix and integrin signalling: the shape of things to come. Biochem J. 1999;339(3):481–488. doi: 10.1042/bj3390481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Liu S, Calderwood DA, Ginsberg MH. Integrin cytoplasmic domain-binding proteins. J Cell Sci. 2000;113(20):3563–3571. doi: 10.1242/jcs.113.20.3563. [DOI] [PubMed] [Google Scholar]
  • 73.Schlaepfer DD, Hauck CR, Sieg DJ. Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999;71:435–478. doi: 10.1016/S0079-6107(98)00052-2. [DOI] [PubMed] [Google Scholar]
  • 74.Parsons JT. Focal adhesion kinase: the first ten years. J Cell Sci. 2003;116(8):1409–1416. doi: 10.1242/jcs.00373. [DOI] [PubMed] [Google Scholar]
  • 75.Young SR, Gerard-O’Riley R, Kim JB, Pavalko FM. Focal adhesion kinase is important for fluid shear stress-induced mechanotransduction in osteoblasts. J Bone Miner Res. 2009;24:411–424. doi: 10.1359/jbmr.081102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Lee JH, Yu HS, Lee GS, Ji A, Hyun JK, Kim HW. Collagen gel three-dimensional matrices combined with adhesive proteins stimulate neuronal differentiation of mesenchymal stem cells. J R Soc Interface. 2011;8:998–1010. doi: 10.1098/rsif.2010.0613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Leucht P, Kim JB, Currey JA, Brunski J, Helms JA. FAK-Mediated mechanotransduction in skeletal regeneration. PLoS One. 2007;2:e390. doi: 10.1371/journal.pone.0000390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Kawarizadeh A, Bourauel C, Götz W, Jäger A. Early responses of periodontal ligament cells to mechanical stimulus in vivo. J Dent Res. 2005;84:902–906. doi: 10.1177/154405910508401006. [DOI] [PubMed] [Google Scholar]
  • 79.Plotkin LI, Mathov I, Aguirre JI, Parfitt AM, Manolagas SC, Bellido T. Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs. Am J Physiol Cell Physiol. 2005;289:C633–C643. doi: 10.1152/ajpcell.00278.2004. [DOI] [PubMed] [Google Scholar]
  • 80.Turner CE. Paxillin and focal adhesion signalling. Nat Cell Biol. 2000;2:E231–E236. doi: 10.1038/35046659. [DOI] [PubMed] [Google Scholar]
  • 81.Brown MC, Turner CE. Paxillin: adapting to change. Physiol Rev. 2004;84:1315–1339. doi: 10.1152/physrev.00002.2004. [DOI] [PubMed] [Google Scholar]
  • 82.Mierke CT. The role of vinculin in the regulation of the mechanical properties of cells. Cell Biochem Biophys. 2009;53:115–126. doi: 10.1007/s12013-009-9047-6. [DOI] [PubMed] [Google Scholar]
  • 83.Kawai S, Enzan H, Hayashi Y, Jin YL, Guo LM, Miyazaki E, et al. Vinculin: a novel marker for quiescent and activated hepatic stellate cells in human and rat livers. Virchows Arch. 2003;443:78–86. doi: 10.1007/s00428-003-0804-4. [DOI] [PubMed] [Google Scholar]
  • 84.Glück U, Rodríguez Fernández JL, Pankov R, Ben-Ze’ev A. Regulation of adherens junction protein expression in growth-activated 3T3 cells and in regenerating liver. Exp Cell Res. 1992;202:477–486. doi: 10.1016/0014-4827(92)90102-E. [DOI] [PubMed] [Google Scholar]
  • 85.Zhang X, Jiang G, Cai Y, Monkley SJ, Critchley DR, Sheetz MP. Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nat Cell Biol. 2008;10:1062–1068. doi: 10.1038/ncb1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Franco SJ, Rodgers MA, Perrin BJ, Han J, Bennin DA, Critchley DR, et al. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol. 2004;6:977–983. doi: 10.1038/ncb1175. [DOI] [PubMed] [Google Scholar]
  • 87.Yan B, Calderwood DA, Yaspan B, Ginsberg MH. Calpain cleavage promotes talin binding to the beta 3 integrin cytoplasmic domain. J Biol Chem. 2001;276:28164–28170. doi: 10.1074/jbc.M104161200. [DOI] [PubMed] [Google Scholar]
  • 88.Tadokoro S, Shattil SJ, Eto K, Tai V, Liddington R, Pereda JM, et al. Talin binding to integrin beta tails: a final common step in integrin activation. Science. 2003;302:103–106. doi: 10.1126/science.1086652. [DOI] [PubMed] [Google Scholar]
  • 89.Liu D, Genetos DC, Shao Y, Geist DJ, Li J, Ke HZ, et al. Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca(2+)-and ATP-dependent in MC3T3-E1 osteoblasts. Bone. 2008;42:644–652. doi: 10.1016/j.bone.2007.09.058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90.Riddle RC, Taylor AF, Genetos DC, Donahue HJ. MAP kinase and calcium signaling mediate fluid flow-induced human mesenchymal stem cell proliferation. Am J Physiol Cell Physiol. 2006;290:C776–C784. doi: 10.1152/ajpcell.00082.2005. [DOI] [PubMed] [Google Scholar]
  • 91.Shin MK, Kim MK, Bae YS, Jo I, Lee SJ, Chung CP, et al. 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. 2008;20:613–624. doi: 10.1016/j.cellsig.2007.11.012. [DOI] [PubMed] [Google Scholar]
  • 92.Haasper C, Jagodzinski M, Drescher M, Meller R, Wehmeier M, Krettek C, et al. Cyclic strain induces FosB and initiates osteogenic differentiation of mesenchymal cells. Exp Toxicol Pathol. 2008;59:355–363. doi: 10.1016/j.etp.2007.11.013. [DOI] [PubMed] [Google Scholar]
  • 93.Iqbal J, Zaidi M. Molecular regulation of mechanotransduction. Biochem Biophys Res Commun. 2005;328:751–755. doi: 10.1016/j.bbrc.2004.12.087. [DOI] [PubMed] [Google Scholar]
  • 94.Fu Q, Wu C, Shen Y, Zheng S, Chen R. Effect of LIMK2 RNAi on reorganization of the actin cytoskeleton in osteoblasts induced by fluid shear stress. J Biomech. 2008;41:3225–3228. doi: 10.1016/j.jbiomech.2008.08.010. [DOI] [PubMed] [Google Scholar]
  • 95.Jaasma MJ, O’Brien FJ. Mechanical stimulation of osteoblasts using steady and dynamic fluid flow. Tissue Eng Part A. 2008;14:1213–1223. doi: 10.1089/ten.tea.2007.0321. [DOI] [PubMed] [Google Scholar]
  • 96.Rodríguez JP, González M, Ríos S, Cambiazo V. Cytoskeletal organization of human mesenchymal stem cells (MSC) changes during their osteogenic differentiation. J Cell Biochem. 2004;93:721–731. doi: 10.1002/jcb.20234. [DOI] [PubMed] [Google Scholar]
  • 97.Arnsdorf EJ, Tummala P, Kwon RY, Jacobs CR. Mechanically induced osteogenic differentiation—the role of RhoA, ROCKII and cytoskeletal dynamics. J Cell Sci. 2009;122(4):546–553. doi: 10.1242/jcs.036293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Patwari P, Lee RT. Mechanical control of tissue morphogenesis. Circ Res. 2008;103:234–243. doi: 10.1161/CIRCRESAHA.108.175331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99.Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179–183. doi: 10.1038/nature10137. [DOI] [PubMed] [Google Scholar]
  • 100.Vu TH, Werb Z. Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev. 2000;14:2123–2133. doi: 10.1101/gad.815400. [DOI] [PubMed] [Google Scholar]
  • 101.Knittel T, Mehde M, Grundmann A, Saile B, Scharf JG, Ramadori G. Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat. Histochem Cell Biol. 2000;113:443–453. doi: 10.1007/s004180000150. [DOI] [PubMed] [Google Scholar]
  • 102.Snyman C, Niesler CU. MMP-14 in skeletal muscle repair. J Muscle Res Cell Motil. 2015;36:215–225. doi: 10.1007/s10974-015-9414-4. [DOI] [PubMed] [Google Scholar]
  • 103.Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005;6:56–68. doi: 10.1038/nrm1549. [DOI] [PubMed] [Google Scholar]
  • 104.Tlatli R, Nozach H, Collet G, Beau F, Vera L, Stura E, et al. Grafting of functional motifs onto protein scaffolds identified by PDB screening—an efficient route to design optimizable protein binders. FEBS J. 2013;280:139–159. doi: 10.1111/febs.12056. [DOI] [PubMed] [Google Scholar]

Articles from Tissue Engineering and Regenerative Medicine are provided here courtesy of Springer

RESOURCES