An Introductory Review of Cell Mechanobiology

Mechanical loads induce changes in the structure, composition, and function of living tissues. Cells in tissues are responsible for these changes, which cause physiological or pathological alterations in the extracellular matrix (ECM). This article provides an introductory review of the mechanobiology of load-sensitive cells in vivo, which include fibroblasts, chondrocytes, osteoblasts, endothelial cells, and smooth muscle cells. Many studies have shown that mechanical loads affect diverse cellular functions, such as cell proliferation, ECM gene and protein expression, and the production of soluble factors. Major cellular components involved in the mechanotransduction mechanisms include the cytoskeleton, integrins, G proteins, receptor tyrosine kinases, mitogen-activated protein kinases, and stretch-activated ion channels. Future research in the area of cell mechanobiology will require novel experimental and theoretical methodologies to determine the type and magnitude of the forces experienced at the cellular and sub-cellular levels and to identify the force sensors/receptors that initiate the cascade of cellular and molecular events

[1]  J. Kimura,et al.  Chondrocyte and chondrosarcoma cell integrins with affinity for collagen type II and their response to mechanical stress. , 1995, Experimental cell research.

[2]  Keiji Naruse,et al.  Involvement of stretch-activated ion channels in Ca2+ mobilization to mechanical stretch in endothelial cells. , 1993, The American journal of physiology.

[3]  T. Borg,et al.  Structural and functional characterisation of cardiac fibroblasts. , 2005, Cardiovascular research.

[4]  F Sachs,et al.  Stretch-sensitive ion channels: an update. , 1992, Society of General Physiologists series.

[5]  L. Cantley,et al.  Oncogenes and signal transduction , 1991, Cell.

[6]  Z. Galis,et al.  This Review Is Part of a Thematic Series on Matrix Metalloproteinases, Which Includes the following Articles: Matrix Metalloproteinase Inhibition after Myocardial Infarction: a New Approach to Prevent Heart Failure? Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: the Good, the Ba , 2022 .

[7]  Jane E. Aubin,et al.  Mesenchymal Stem Cells and Osteoblast Differentiation , 2008 .

[8]  Thiennu H. Vu,et al.  Matrix metalloproteinases: effectors of development and normal physiology. , 2000, Genes & development.

[9]  L. Matrisian,et al.  Matrix metalloproteinases: they're not just for matrix anymore! , 2001, Current opinion in cell biology.

[10]  Z. Werb,et al.  ECM signalling: orchestrating cell behaviour and misbehaviour. , 1998, Trends in cell biology.

[11]  R. Timpl,et al.  The collagen superfamily. , 1995, International archives of allergy and immunology.

[12]  A. Zeiher,et al.  Shear Stress–Induced Endothelial Cell Migration Involves Integrin Signaling Via the Fibronectin Receptor Subunits α5 and β1 , 2002 .

[13]  Y. Yazaki,et al.  Mechanical stretch activates the stress‐activated protein kinase in cardiac myocytes , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  Jennifer S. Park,et al.  Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells , 2004, Biotechnology and bioengineering.

[15]  M. van Griensven,et al.  Modulation of cell functions of human tendon fibroblasts by different repetitive cyclic mechanical stress patterns. , 2003, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[16]  A. Poole Proteoglycans in health and disease: structures and functions. , 1986, The Biochemical journal.

[17]  Richard T. Lee,et al.  Mechanical Strain Induces Specific Changes in the Synthesis and Organization of Proteoglycans by Vascular Smooth Muscle Cells* , 2001, The Journal of Biological Chemistry.

[18]  M. Karin Signal transduction from cell surface to nucleus in development and disease , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  K. Guntupalli,et al.  Respiratory failure in interstitial lung disease , 2004, Current opinion in pulmonary medicine.

[20]  R. Duncan,et al.  Human osteoblast-like cells respond to mechanical strain with increased bone matrix protein production independent of hormonal regulation. , 1995, Endocrinology.

[21]  R. Ross The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[22]  F Sachs,et al.  Stretch-activated ion channels in tissue-cultured chick heart. , 1993, The American journal of physiology.

[23]  O. Hamill,et al.  Molecular basis of mechanotransduction in living cells. , 2001, Physiological reviews.

[24]  A. Grodzinsky,et al.  Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression. , 2003, Journal of biomedical materials research. Part A.

[25]  F. Silver,et al.  Mechanobiology of force transduction in dermal tissue , 2003, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[26]  Robert M. Nerem,et al.  Dynamic Mechanical Conditioning of Collagen-Gel Blood Vessel Constructs Induces Remodeling In Vitro , 2000, Annals of Biomedical Engineering.

[27]  B. Nebe,et al.  Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. , 1996, European journal of cell biology.

[28]  K. Kadler,et al.  Collagen fibril biosynthesis in tendon: a review and recent insights. , 2002, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[29]  C. Hébert,et al.  Interleukin-8: a review. , 1993, Cancer investigation.

[30]  Albert J Banes,et al.  Novel system for engineering bioartificial tendons and application of mechanical load. , 2003, Tissue engineering.

[31]  A. Rot,et al.  In vitro and in vivo activity and pathophysiology of human interleukin-8 and related peptides. , 1993, International review of experimental pathology.

[32]  R. Bizios,et al.  Morphological and proliferative responses of endothelial cells to hydrostatic pressure: Role of fibroblast growth factor , 1993, Journal of cellular physiology.

[33]  Yasuteru Muragaki,et al.  Stretch-Induced Collagen Synthesis in Cultured Smooth Muscle Cells from Rabbit Aortic Media and a Possible Involvement of Angiotensin II and Transforming Growth Factor-β , 1998, Journal of Vascular Research.

[34]  Gerald A. Meininger,et al.  Shear Stress-induced Release of Basic Fibroblast Growth Factor from Endothelial Cells Is Mediated by Matrix Interaction via Integrin αVβ3 * , 2002, The Journal of Biological Chemistry.

[35]  Joe Tien,et al.  Mechanotransduction at cell-matrix and cell-cell contacts. , 2004, Annual review of biomedical engineering.

[36]  D Kaspar,et al.  Dynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity. , 2000, Journal of biomechanics.

[37]  Van C. Mow,et al.  Cell Mechanics and Cellular Engineering , 2011, Springer New York.

[38]  Z. Werb,et al.  How matrix metalloproteinases regulate cell behavior. , 2001, Annual review of cell and developmental biology.

[39]  L. Vaughan,et al.  Cartilage contains mixed fibrils of collagen types II, IX, and XI , 1989, The Journal of cell biology.

[40]  M. Kirber,et al.  Multiple pathways responsible for the stretch‐induced increase in Ca2+ concentration in toad stomach smooth muscle cells , 2000, The Journal of physiology.

[41]  C F Dewey,et al.  Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells. , 1992, The American journal of physiology.

[42]  E. Wagner,et al.  Reaching a genetic and molecular understanding of skeletal development. , 2002, Developmental cell.

[43]  S. Woo,et al.  Mechanical properties of tendons and ligaments. II. The relationships of immobilization and exercise on tissue remodeling. , 1982, Biorheology.

[44]  C. Turner,et al.  Mechanotransduction and functional response of the skeleton to physical stress: The mechanisms and mechanics of bone adaptation , 1998, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[45]  M. Aumailley,et al.  Structure and biological activity of the extracellular matrix , 1998, Journal of Molecular Medicine.

[46]  S. Goldstein,et al.  Effect of compressive loading on chondrocyte differentiation in agarose cultures of chick limb‐bud cells , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[47]  E Ruoslahti,et al.  Integrin signaling. , 1999, Science.

[48]  B. Williams Mechanical influences on vascular smooth muscle cell function , 1998, Journal of hypertension.

[49]  D. Eyre,et al.  Collagens and cartilage matrix homeostasis. , 2004, Clinical orthopaedics and related research.

[50]  C Neidlinger-Wilke,et al.  Cyclic stretching of human osteoblasts affects proliferation and metabolism: A new experimental method and its application , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[51]  A. Zeiher,et al.  Shear Stress‐Induced Endothelial Cell Migration Involves Integrin Signaling Via the Fibronectin Receptor Subunits &agr;5 and &bgr;1 , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[52]  H. Ueno,et al.  Mechanical stretch stimulates growth of vascular smooth muscle cells via epidermal growth factor receptor. , 2000, American journal of physiology. Heart and circulatory physiology.

[53]  P. Libby,et al.  Transcriptional profile of mechanically induced genes in human vascular smooth muscle cells. , 1999, Circulation research.

[54]  Jeremy J Mao,et al.  Growth and development: hereditary and mechanical modulations. , 2004, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[55]  L. Matrisian,et al.  Matrix metalloproteinases: multifunctional contributors to tumor progression. , 2000, Molecular medicine today.

[56]  E. Grood,et al.  The Strain Magnitude and Contact Guidance Determine Orientation Response of Fibroblasts to Cyclic Substrate Strains , 2000, Connective tissue research.

[57]  J. Wang,et al.  Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions. , 2004, Journal of biomechanics.

[58]  Steven A. Goldstein,et al.  Chondrocyte Differentiation is Modulated by Frequency and Duration of Cyclic Compressive Loading , 2001, Annals of Biomedical Engineering.

[59]  P. Howard,et al.  Compression and Tension: Differential Effects on Matrix Accumulation by Periodontal Ligament Fibroblasts In Vitro , 2004, Connective tissue research.

[60]  Joseph Schlessinger,et al.  Signal transduction by receptors with tyrosine kinase activity , 1990, Cell.

[61]  Ulrich Bosch,et al.  Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts , 2001, European Journal of Applied Physiology.

[62]  R. Derynck,et al.  Toward a molecular understanding of skeletal development , 1995, Cell.

[63]  H. Verheul,et al.  Vascular endothelial growth factor and its inhibitors. , 2003, Drugs of today.

[64]  M. Cobb,et al.  Extracellular signal-regulated kinases: ERKs in progress. , 1991, Cell regulation.

[65]  C. Dinarello,et al.  The IL-1 family and inflammatory diseases. , 2002, Clinical and experimental rheumatology.

[66]  P. Howard,et al.  Mechanical forces alter extracellular matrix synthesis by human periodontal ligament fibroblasts. , 2010, Journal of periodontal research.

[67]  S Glagov,et al.  Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. , 2003, Science.

[68]  A. Grodzinsky,et al.  Mechanical Regulation of Mitogen-activated Protein Kinase Signaling in Articular Cartilage* , 2003, Journal of Biological Chemistry.

[69]  T. Krieg,et al.  Laminins: a family of diverse multifunctional molecules of basement membranes. , 1996, The Journal of investigative dermatology.

[70]  R. Bank,et al.  Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. , 2002, Matrix biology : journal of the International Society for Matrix Biology.

[71]  P. Libby,et al.  Small Mechanical Strains Selectively Suppress Matrix Metalloproteinase-1 Expression by Human Vascular Smooth Muscle Cells* , 1998, Journal of Biological Chemistry.

[72]  J. Frangos,et al.  Equibiaxial strain and strain rate stimulate early activation of G proteins in cardiac fibroblasts. , 1998, American journal of physiology. Cell physiology.

[73]  D. Bader,et al.  Influence of external uniaxial cyclic strain on oriented fibroblast-seeded collagen gels. , 2003, Tissue engineering.

[74]  R. Iozzo Matrix proteoglycans: from molecular design to cellular function. , 1998, Annual review of biochemistry.

[75]  M. Tanzer,et al.  Aggrecan from start to finish , 2000, Journal of Bone and Mineral Metabolism.

[76]  A. Grodzinsky,et al.  Cartilage tissue remodeling in response to mechanical forces. , 2000, Annual review of biomedical engineering.

[77]  E. Grood,et al.  Cell orientation response to cyclically deformed substrates: experimental validation of a cell model. , 1995, Journal of biomechanics.

[78]  M. Chiquet,et al.  Induction of tenascin-C by cyclic tensile strain versus growth factors: distinct contributions by Rho/ROCK and MAPK signaling pathways. , 2004, Biochimica et biophysica acta.

[79]  K. Suzuki,et al.  Matrix metalloproteinases degrade insulin-like growth factor-binding protein-3 in dermal fibroblast cultures. , 1994, The Journal of biological chemistry.

[80]  Albert C. Chen,et al.  Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[81]  J. Sadoshima,et al.  The cellular and molecular response of cardiac myocytes to mechanical stress. , 1997, Annual review of physiology.

[82]  Mone Zaidi,et al.  Molecular regulation of mechanotransduction. , 2005, Biochemical and biophysical research communications.

[83]  H. Hämmerle,et al.  Orientation response of arterial smooth muscle cells to mechanical stimulation. , 1986, European journal of cell biology.

[84]  J. Finkelstein,et al.  Mechanical strain-induced proliferation and signaling in pulmonary epithelial H441 cells. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[85]  C. Overall Molecular determinants of metalloproteinase substrate specificity , 2002, Molecular biotechnology.

[86]  R. Visse,et al.  This Review Is Part of a Thematic Series on Matrix Metalloproteinases, Which Includes the following Articles: Matrix Metalloproteinase Inhibition after Myocardial Infarction: a New Approach to Prevent Heart Failure? Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: the Good, the Ba , 2022 .

[87]  F H Silver,et al.  Analysis of mammalian connective tissue: relationship between hierarchical structures and mechanical properties. , 1992, Journal of long-term effects of medical implants.

[88]  T. Krieg,et al.  Regulation of connective tissue homeostasis in the skin by mechanical forces. , 2004, Clinical and experimental rheumatology.

[89]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[90]  D. R. Carter,et al.  In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[91]  Chad Johnson,et al.  Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells. , 2003, American journal of physiology. Heart and circulatory physiology.

[92]  C. Turner,et al.  Mechanotransduction and the functional response of bone to mechanical strain , 1995, Calcified Tissue International.

[93]  Nobuyuki Itoh,et al.  Fibroblast growth factors , 2001, Genome Biology.

[94]  M. B. Mathews Connective tissue. Macromolecular structure and evolution. , 1975, Molecular biology, biochemistry, and biophysics.

[95]  B. Sumpio,et al.  Cells in focus: endothelial cell. , 2002, The international journal of biochemistry & cell biology.

[96]  Gerard A. Ateshian,et al.  Influence of Seeding Density and Dynamic Deformational Loading on the Developing Structure/Function Relationships of Chondrocyte-Seeded Agarose Hydrogels , 2002, Annals of Biomedical Engineering.

[97]  N. Smyth,et al.  The role of laminins in basement membrane function , 1998, Journal of anatomy.

[98]  T. Borg,et al.  Collagen expression in mechanically stimulated cardiac fibroblasts. , 1991, Circulation research.

[99]  T. Kulik,et al.  Effect of stretch on growth and collagen synthesis in cultured rat and lamb pulmonary arterial smooth muscle cells , 1993, Journal of cellular physiology.

[100]  D. Murray,et al.  The effect of strain on bone cell prostaglandin E2 release: A new experimental method , 1990, Calcified Tissue International.

[101]  A. Banes,et al.  PDGF-BB, IGF-I and mechanical load stimulate DNA synthesis in avian tendon fibroblasts in vitro. , 1995, Journal of biomechanics.

[102]  R. Stockwell Biology of cartilage cells , 1979 .

[103]  P. Davies,et al.  Flow-mediated endothelial mechanotransduction. , 1995, Physiological reviews.

[104]  S. Haskill,et al.  Signal transduction from the extracellular matrix , 1993, The Journal of cell biology.

[105]  G Riley,et al.  Multiple changes in gene expression in chronic human Achilles tendinopathy. , 2001, Matrix biology : journal of the International Society for Matrix Biology.

[106]  Carine Michiels,et al.  Endothelial cell functions , 2003, Journal of cellular physiology.

[107]  Y. Okada,et al.  Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release. , 1997, The Biochemical journal.

[108]  D R Carter,et al.  Effects of shear stress on articular chondrocyte metabolism. , 2000, Biorheology.

[109]  Anne J. Ridley,et al.  The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors , 1992 .

[110]  J. Hoyer,et al.  Stretch‐activated cation channel in human umbilical vein endothelium in normal pregnancy and in preeclampsia , 1998, Journal of hypertension.

[111]  S. Kondo,et al.  Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells. , 1996, The Journal of clinical investigation.

[112]  R. Marquet,et al.  Interleukin-6: historical background, genetics and biological significance. , 1990, Immunology letters.

[113]  E. Herrold,et al.  Heart failure in aortic regurgitation: the role of primary fibrosis and its cellular and molecular pathophysiology. , 2004, Advances in cardiology.

[114]  D. Bader,et al.  Temporal regulation of chondrocyte metabolism in agarose constructs subjected to dynamic compression. , 2003, Archives of biochemistry and biophysics.

[115]  N. Resnick,et al.  Hemodynamic forces are complex regulators of endothelial gene expression , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[116]  D. Carey,et al.  Localization of a heterotrimeric G protein gamma subunit to focal adhesions and associated stress fibers , 1994, The Journal of cell biology.

[117]  T. Kishimoto,et al.  Inhibition of IL-6 for the treatment of inflammatory diseases. , 2004, Current opinion in pharmacology.

[118]  Nancy Y. Ip,et al.  ERKs: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF , 1991, Cell.

[119]  T Delhaas,et al.  Differential responses of adult cardiac fibroblasts to in vitro biaxial strain patterns. , 1999, Journal of molecular and cellular cardiology.

[120]  R. Mecham,et al.  Extracellular matrix assembly and structure , 1994 .

[121]  M. Cobb,et al.  ERKs, extracellular signal-regulated MAP-2 kinases. , 1991, Current opinion in cell biology.

[122]  F. Yin,et al.  Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. , 2001, Journal of biomechanics.

[123]  L. Bonassar,et al.  A role for the interleukin-1 receptor in the pathway linking static mechanical compression to decreased proteoglycan synthesis in surface articular cartilage. , 2003, Archives of biochemistry and biophysics.

[124]  D. Ingber,et al.  Integrins as mechanochemical transducers. , 1991, Current opinion in cell biology.

[125]  H. Hämmerle,et al.  Orientation of cultured arterial smooth muscle cells growing on cyclically stretched substrates. , 1986, Acta anatomica.

[126]  Nitzan Resnick,et al.  Fluid shear stress and the vascular endothelium: for better and for worse. , 2003, Progress in biophysics and molecular biology.

[127]  G. Owens,et al.  Role of mechanical strain in regulation of differentiation of vascular smooth muscle cells. , 1996, Circulation research.

[128]  A. Ooshima,et al.  Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angiotensin system and platelet-derived growth factor (PDGF). , 1997, Hypertension research : official journal of the Japanese Society of Hypertension.

[129]  M. Baggiolini,et al.  Interleukin‐8, a chemotactic and inflammatory cytokine , 1992, FEBS letters.

[130]  D. Ingber,et al.  Mechanotransduction across the cell surface and through the cytoskeleton , 1993 .

[131]  F M Watt,et al.  Regulation of development and differentiation by the extracellular matrix. , 1993, Development.

[132]  Robert M Nerem,et al.  Mechanical compression alters gene expression and extracellular matrix synthesis by chondrocytes cultured in collagen I gels. , 2002, Biomaterials.

[133]  U Bosch,et al.  The Proliferative Response of Isolated Human Tendon Fibroblasts to Cyclic Biaxial Mechanical Strain * , 2000, The American journal of sports medicine.

[134]  Millie Hughes-Fulford,et al.  Signal Transduction and Mechanical Stress , 2004, Science's STKE.

[135]  S. Chien,et al.  Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[136]  K. Sipos,et al.  Differential Effect of Shear Stress on Extracellular Signal-regulated Kinase and N-terminal Jun Kinase in Endothelial Cells , 1997, The Journal of Biological Chemistry.

[137]  A. Seth,et al.  Transcriptional Regulation of a Contractile Gene by Mechanical Forces Applied through Integrins in Osteoblasts* , 2002, The Journal of Biological Chemistry.

[138]  J. Frangos,et al.  Strain and strain rate activation of G proteins in human endothelial cells. , 2002, Biochemical and biophysical research communications.

[139]  P. Parker,et al.  Integrin-specific signaling pathways controlling focal adhesion formation and cell migration , 2003, The Journal of cell biology.

[140]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[141]  W. Durante,et al.  Physiological cyclic stretch directs L‐arginine transport and metabolism to collagen synthesis in vascular smooth muscle , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[142]  D. Hayoz,et al.  Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[143]  K. Doane,et al.  Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. , 1990, Journal of cell science.

[144]  C. S. Chen,et al.  Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[145]  Ivan Stamenkovic,et al.  Functional structure and composition of the extracellular matrix , 2003, The Journal of pathology.

[146]  D. Burr,et al.  Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. , 1998, American journal of physiology. Cell physiology.

[147]  M. Toborek,et al.  Endothelial cell functions.¶Relationship to atherogenesis , 1999, Basic Research in Cardiology.

[148]  E. Ruoslahti Structure and biology of proteoglycans. , 1988, Annual review of cell biology.

[149]  K Takahashi,et al.  Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL-1beta expression resulting in chondrogenesis in mouse embryonic limb bud mesenchymal cells. , 1998, Journal of cell science.

[150]  Z. Werb,et al.  Extracellular Matrix Remodeling during Morphogenesis a , 1998, Annals of the New York Academy of Sciences.

[151]  S. Woo,et al.  Mechanical properties of tendons and ligaments. I. Quasi-static and nonlinear viscoelastic properties. , 1982, Biorheology.

[152]  H. Lijnen Metalloproteinases in Development and Progression of Vascular Disease , 2003, Pathophysiology of Haemostasis and Thrombosis.

[153]  D. Hulmes,et al.  The collagen superfamily--diverse structures and assemblies. , 1992, Essays in biochemistry.

[154]  M. Laberge,et al.  In vitro strain-induced endothelial cell dysfunction determined by DNA synthesis , 2003, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[155]  H. Helminen,et al.  Effects of cyclic hydrostatic pressure on proteoglycan synthesis in cultured chondrocytes and articular cartilage explants. , 1993, Archives of biochemistry and biophysics.

[156]  Robert M. Nerem,et al.  The Role of Matrix Metalloproteinase-2 in the Remodeling of Cell-Seeded Vascular Constructs Subjected to Cyclic Strain , 2001, Annals of Biomedical Engineering.

[157]  F. Villarreal,et al.  Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen. , 1992, The American journal of physiology.

[158]  A. Grodzinsky,et al.  Combined effects of dynamic tissue shear deformation and insulin-like growth factor I on chondrocyte biosynthesis in cartilage explants. , 2003, Archives of biochemistry and biophysics.

[159]  H. Petite,et al.  Cell mechanotransduction and interactions with biological tissues. , 2000, Biorheology.

[160]  D E Ingber,et al.  Cellular control lies in the balance of forces. , 1998, Current opinion in cell biology.

[161]  I. Stamenkovic,et al.  Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. , 2000, Genes & development.

[162]  J. Frangos,et al.  Fluid flow rapidly activates G proteins in human endothelial cells. Involvement of G proteins in mechanochemical signal transduction. , 1996, Circulation research.

[163]  Z. Werb,et al.  Regulation of matrix biology by matrix metalloproteinases. , 2004, Current opinion in cell biology.

[164]  L. Bonassar,et al.  The effect of dynamic compression on the response of articular cartilage to insulin‐like growth factor‐I , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[165]  D. Ingber Tensegrity: the architectural basis of cellular mechanotransduction. , 1997, Annual review of physiology.

[166]  P. Cahill,et al.  Cyclic strain-mediated regulation of endothelial matrix metalloproteinase-2 expression and activity. , 2004, Cardiovascular research.

[167]  D A Lauffenburger,et al.  Integrin-cytoskeletal interactions in migrating fibroblasts are dynamic, asymmetric, and regulated , 1993, The Journal of cell biology.

[168]  Steven M. Holland,et al.  Mechanical Stretch Enhances mRNA Expression and Proenzyme Release of Matrix Metalloproteinase‐2 (MMP‐2) via NAD(P)H Oxidase‐Derived Reactive Oxygen Species , 2003, Circulation research.

[169]  F. Yin,et al.  Leukotrienes and tyrosine phosphorylation mediate stretching-induced actin cytoskeletal remodeling in endothelial cells. , 2000, Cell motility and the cytoskeleton.

[170]  B. Sumpio,et al.  Effects of cyclic strain on vascular cells. , 2004, Endothelium : journal of endothelial cell research.

[171]  G A Ateshian,et al.  Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. , 2000, Journal of biomechanical engineering.

[172]  L. Bonassar,et al.  Mechanical and physicochemical regulation of the action of insulin-like growth factor-I on articular cartilage. , 2000, Archives of biochemistry and biophysics.

[173]  S. Albelda,et al.  Integrins and other cell adhesion molecules , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[174]  G. Laurent,et al.  Mechanical load enhances the stimulatory effect of PDGF on pulmonary artery fibroblast procollagen synthesis. , 1998, Chest.

[175]  G. Osol Mechanotransduction by vascular smooth muscle. , 1995, Journal of vascular research.

[176]  R. Nagai,et al.  Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes. , 1993, The Journal of biological chemistry.

[177]  G. Ateshian,et al.  The role of cell seeding density and nutrient supply for articular cartilage tissue engineering with deformational loading. , 2003, Osteoarthritis and cartilage.

[178]  M G Mullender,et al.  Mechanobiology of bone tissue. , 2005, Pathologie-biologie.

[179]  E B Hunziker,et al.  Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. , 1995, Journal of cell science.

[180]  C. Tipton,et al.  Experimental studies on the influences of physical activity on ligaments, tendons and joints: a brief review. , 2009, Acta medica Scandinavica. Supplementum.

[181]  Lutz Claes,et al.  Proliferation of human-derived osteoblast-like cells depends on the cycle number and frequency of uniaxial strain. , 2002, Journal of biomechanics.

[182]  T. Aigner,et al.  Collagens--major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair. , 2003, Advanced drug delivery reviews.

[183]  Bao-Wei Wang,et al.  Induction of matrix metalloproteinases-14 and -2 by cyclical mechanical stretch is mediated by tumor necrosis factor-α in cultured human umbilical vein endothelial cells , 2003 .

[184]  D. Ingber Cellular basis of mechanotransduction. , 1998, The Biological bulletin.

[185]  H. Uramoto,et al.  Regulatory mechanisms for the expression and activity of platelet-derived growth factor receptor. , 2003, Acta biochimica Polonica.

[186]  Torsten Gloe,et al.  Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via integrin alpha(v)beta3. , 2002, The Journal of biological chemistry.

[187]  D. Jones,et al.  Biochemical signal transduction of mechanical strain in osteoblast-like cells. , 1991, Biomaterials.

[188]  P. Libby,et al.  Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. , 1994, Circulation research.

[189]  Christopher J. O’Callaghan,et al.  Mechanical Strain–Induced Extracellular Matrix Production by Human Vascular Smooth Muscle Cells: Role of TGF-&bgr;1 , 2000, Hypertension.

[190]  F. Sachs,et al.  Calcium imaging of mechanically induced fluxes in tissue-cultured chick heart: role of stretch-activated ion channels. , 1992, The American journal of physiology.

[191]  R. Kamm,et al.  Mechanotransduction in Cardiac Myocytes , 2004, Annals of the New York Academy of Sciences.

[192]  Gerard A Ateshian,et al.  Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering. , 2003, Tissue engineering.

[193]  Akiko Ueno,et al.  Mechanical stretch augments PDGF receptor β expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells , 2000, Molecular and Cellular Biochemistry.

[194]  James R. Mensch,et al.  Domain organization, genomic structure, evolution, and regulation of expression of the aggrecan gene family. , 1999, Progress in nucleic acid research and molecular biology.

[195]  S. Izumo,et al.  Control of endothelial cell gene expression by flow. , 1995, Journal of biomechanics.

[196]  R. Ross The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.

[197]  Matthias Chiquet,et al.  Tenascins: regulation and putative functions during pathological stress , 2003, The Journal of pathology.

[198]  B. Toole,et al.  Hyaluronan: from extracellular glue to pericellular cue , 2004, Nature Reviews Cancer.

[199]  M. Tsuzaki,et al.  IL‐1β sensitizes intervertebral disc annulus cells to fluid‐induced shear stress , 2001, Journal of cellular biochemistry.

[200]  S. Dedhar,et al.  Bi-directional signal transduction by integrin receptors. , 2000, The international journal of biochemistry & cell biology.

[201]  D. Mackenna,et al.  Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis. , 2000, Cardiovascular research.

[202]  A. Banes,et al.  Enhanced collagen production by smooth muscle cells during repetitive mechanical stretching. , 1988, Archives of surgery.

[203]  J J Fredberg,et al.  Pharmacological activation changes stiffness of cultured human airway smooth muscle cells. , 1996, The American journal of physiology.

[204]  M. E. van der Rest,et al.  Collagen family of proteins , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[205]  R L Juliano,et al.  Cell adhesion molecules, signal transduction and cell growth. , 1999, Current opinion in cell biology.

[206]  M. Chao Growth factor signaling: Where is the specificity? , 1992, Cell.

[207]  Donald E Ingber,et al.  Mechanobiology and diseases of mechanotransduction , 2003, Annals of medicine.

[208]  Motoharu Seiki,et al.  The cell surface: the stage for matrix metalloproteinase regulation of migration. , 2002, Current opinion in cell biology.

[209]  K. Ng,et al.  Cell lines and primary cell cultures in the study of bone cell biology , 2004, Molecular and Cellular Endocrinology.

[210]  David J. Mooney,et al.  Cyclic mechanical strain regulates the development of engineered smooth muscle tissue , 1999, Nature Biotechnology.

[211]  F. Iannone,et al.  The pathophysiology of osteoarthritis , 2003, Aging clinical and experimental research.

[212]  W. Akeson,et al.  Time‐dependent increases in type‐III collagen gene expression in medial collateral ligament fibroblasts under cyclic strains , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[213]  E. Mackie,et al.  Osteoblasts: novel roles in orchestration of skeletal architecture. , 2003, The international journal of biochemistry & cell biology.

[214]  W. Herzog,et al.  Stretch and interleukin‐1β induce matrix metalloproteinases in rabbit tendon cells in vitro , 2002 .

[215]  S. Schwartz,et al.  Pharmacology of smooth muscle cell replication. , 1992, Hypertension.

[216]  E Ruoslahti,et al.  Extracellular signal-regulated kinase and c-Jun NH2-terminal kinase activation by mechanical stretch is integrin-dependent and matrix-specific in rat cardiac fibroblasts. , 1998, The Journal of clinical investigation.

[217]  M. Schwartz,et al.  Integrins in Mechanotransduction* , 2004, Journal of Biological Chemistry.

[218]  David L. Brautigan,et al.  Raf-1 activates MAP kinase-kinase , 1992, Nature.

[219]  K. Kurokawa,et al.  Tyrosine-kinase dependent TGF-beta and extracellular matrix expression by mechanical stretch in vascular smooth muscle cells. , 2000, Hypertension research : official journal of the Japanese Society of Hypertension.

[220]  E. Breen Mechanical strain increases type I collagen expression in pulmonary fibroblasts in vitro. , 2000, Journal of applied physiology.

[221]  H. Ives,et al.  Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. , 1995, The Journal of clinical investigation.

[222]  David A Weitz,et al.  Dealing with mechanics: mechanisms of force transduction in cells. , 2004, Trends in biochemical sciences.

[223]  J D Humphrey,et al.  Stress, strain, and mechanotransduction in cells. , 2001, Journal of biomechanical engineering.

[224]  J. Williams,et al.  The inositol phosphate pathway as a mediator in the proliferative response of rat calvarial bone cells to cyclical biaxial mechanical strain , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[225]  J. Wang Mechanobiology of tendon. , 2006, Journal of biomechanics.

[226]  J. Bishop,et al.  Mechanical load enhances the stimulatory effect of serum growth factors on cardiac fibroblast procollagen synthesis. , 1997, Journal of molecular and cellular cardiology.

[227]  M. Chiquet,et al.  Regulation of extracellular matrix gene expression by mechanical stress. , 1999, Matrix biology : journal of the International Society for Matrix Biology.