Mechanobiology of adult and stem cells.

Mechanical forces, including gravity, tension, compression, hydrostatic pressure, and fluid shear stress, play a vital role in human physiology and pathology. They particularly influence extracellular matrix (ECM) gene expression, ECM protein synthesis, and production of inflammatory mediators of many load-sensitive adult cells such as fibroblasts, chondrocytes, smooth muscle cells, and endothelial cells. Furthermore, the mechanical forces generated by cells themselves, known as cell traction forces (CTFs), also influence many biological processes such as wound healing, angiogenesis, and metastasis. Thus, the quantitative characterization of CTFs by qualities such as magnitude and distribution is useful for understanding physiological and pathological events at the tissue and organ levels. Recently, the effects of mechanical loads on embryonic and adult stem cells in terms of self-renewal, differentiation, and matrix protein expression have been investigated. While it seems certain that mechanical loads applied to stem cells regulate their self-renewal and induce controlled cell lineage differentiation, the detailed molecular signaling mechanisms responsible for these mechano-effects remain to be elucidated. Challenges in the fields of both adult- and stem-cell mechanobiology include devising novel experimental and theoretical methodologies to examine mechano-responses more closely to various forms of mechanical forces and mechanotransduction mechanisms of these cells in a more physiologically accurate setting. Such novel methodologies will lead to better understanding of various pathological diseases, their management, and translational applications in the ever expanding field of tissue engineering.

[1]  Elizabeth G Loboa,et al.  Osteogenic differentiation of human mesenchymal stem cells in collagen matrices: effect of uniaxial cyclic tensile strain on bone morphogenetic protein (BMP-2) mRNA expression. , 2006, Tissue engineering.

[2]  Immanuel M. Sebastine,et al.  The Role of Mechanical Stimulation in Engineering of Extracellular Matrix (ECM) , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[3]  L. Addadi,et al.  Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates , 2001, Nature Cell Biology.

[4]  D. Vorp,et al.  Characterization of the response of bone marrow-derived progenitor cells to cyclic strain: implications for vascular tissue-engineering applications. , 2004, Tissue engineering.

[5]  Benjamin Geiger,et al.  Exploring the Neighborhood Adhesion-Coupled Cell Mechanosensors , 2002, Cell.

[6]  Aaditya C Devkota,et al.  Cyclic loading alters biomechanical properties and secretion of PGE2 and NO from tendon explants. , 2006, Clinical biomechanics.

[7]  K. Burridge,et al.  Rho-stimulated contractility drives the formation of stress fibers and focal adhesions , 1996, The Journal of cell biology.

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

[9]  N. K. Wessells,et al.  Morphogenetic rearrangement of injected collagen in developing chicken limb buds. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  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.

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

[12]  S. Suresh,et al.  Cell and molecular mechanics of biological materials , 2003, Nature materials.

[13]  Stuart B Goodman,et al.  Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro. , 2006, Tissue engineering.

[14]  Donald E Ingber,et al.  Control of basement membrane remodeling and epithelial branching morphogenesis in embryonic lung by Rho and cytoskeletal tension , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[15]  F. Marceau,et al.  International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences , 2005, Pharmacological Reviews.

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

[17]  B. Hinz,et al.  Myofibroblasts and mechano-regulation of connective tissue remodelling , 2002, Nature Reviews Molecular Cell Biology.

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

[19]  A I Caplan,et al.  In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. , 1998, Experimental cell research.

[20]  M S Kolodney,et al.  Isometric contraction by fibroblasts and endothelial cells in tissue culture: a quantitative study , 1992, The Journal of cell biology.

[21]  A. Phillips,et al.  TGF-beta1-mediated fibroblast-myofibroblast terminal differentiation-the role of Smad proteins. , 2003, Experimental cell research.

[22]  D. Schurman,et al.  Mechanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  S. Jimenez,et al.  CCAAT binding transcription factor binds and regulates human COL1A1 promoter activity in human dermal fibroblasts: demonstration of increased binding in systemic sclerosis fibroblasts. , 2000, Arthritis and rheumatism.

[24]  S. J. Chen,et al.  Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3. , 1999, The Journal of investigative dermatology.

[25]  Kenneth M. Yamada,et al.  Cell interactions with three-dimensional matrices. , 2002, Current opinion in cell biology.

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

[27]  Qing-Ming Wang,et al.  Cell shape regulates collagen type I expression in human tendon fibroblasts. , 2008, Cell motility and the cytoskeleton.

[28]  B. H. Campbell,et al.  A multi-station culture force monitor system to study cellular contractility. , 2003, Journal of biomechanics.

[29]  Micah Dembo,et al.  Focal adhesion kinase is involved in mechanosensing during fibroblast migration , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. Atala,et al.  Biomaterials for tissue engineering , 2000, World Journal of Urology.

[31]  H. Ives,et al.  Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells. , 1996, Circulation research.

[32]  P. Ragan,et al.  Down‐regulation of chondrocyte aggrecan and type‐II Collagen gene expression correlates with increases in static compression magnitude and duration , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[33]  Jennifer S. Park,et al.  Mechanobiology of mesenchymal stem cells and their use in cardiovascular repair. , 2007, Frontiers in bioscience : a journal and virtual library.

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

[35]  Milan Mrksich,et al.  Micropatterned Surfaces for Control of Cell Shape, Position, and Function , 1998, Biotechnology progress.

[36]  Payam Akhyari,et al.  Mechanical Stretch Regimen Enhances the Formation of Bioengineered Autologous Cardiac Muscle Grafts , 2002, Circulation.

[37]  J. Wang,et al.  Alpha-smooth muscle actin expression enhances cell traction force. , 2007, Cell motility and the cytoskeleton.

[38]  M. Peters-Golden,et al.  Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E. prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation. , 2003, American journal of respiratory cell and molecular biology.

[39]  S. Chien,et al.  Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression , 2002, The EMBO journal.

[40]  M. Dembo,et al.  Stresses at the cell-to-substrate interface during locomotion of fibroblasts. , 1999, Biophysical journal.

[41]  Juan J de Pablo,et al.  Inhibition of human embryonic stem cell differentiation by mechanical strain , 2006, Journal of cellular physiology.

[42]  J. Connelly,et al.  Dynamic Compression Regulates the Expression and Synthesis of Chondrocyte‐Specific Matrix Molecules in Bone Marrow Stromal Cells , 2007, Stem cells.

[43]  H. Im,et al.  Repetitive mechanical stretching modulates IL-1beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts. , 2005, Gene.

[44]  J. Wang,et al.  Healing and Normal Fibroblasts Exhibit Differential Proliferation, Collagen Production, α-SMA Expression, and Contraction , 2006, Annals of Biomedical Engineering.

[45]  H. Cheung,et al.  Cyclic compression maintains viability and induces chondrogenesis of human mesenchymal stem cells in fibrin gel scaffolds. , 2009, Stem cells and development.

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

[47]  M. Carlson,et al.  Release of mechanical tension triggers apoptosis of human fibroblasts in a model of regressing granulation tissue. , 1999, Experimental cell research.

[48]  J. Deschner,et al.  Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals. , 2004, Arthritis and rheumatism.

[49]  Kimiko Yamamoto,et al.  Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro. , 2005, American journal of physiology. Heart and circulatory physiology.

[50]  A. Zeiher,et al.  Shear stress inhibits H2O2-induced apoptosis of human endothelial cells by modulation of the glutathione redox cycle and nitric oxide synthase. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[51]  A. Banes,et al.  A new vacuum-operated stress-providing instrument that applies static or variable duration cyclic tension or compression to cells in vitro. , 1985, Journal of cell science.

[52]  H. Im,et al.  EP4 receptor regulates collagen type-I, MMP-1, and MMP-3 gene expression in human tendon fibroblasts in response to IL-1 beta treatment. , 2007, Gene.

[53]  Ivan Martin,et al.  The FASEB Journal express article 10.1096/fj.01-0656fje. Published online December 28, 2001. Cell differentiation by mechanical stress , 2022 .

[54]  C. Frank,et al.  Healing of the medial collateral ligament of the knee. A morphological and biochemical assessment in rabbits. , 1983, Acta orthopaedica Scandinavica.

[55]  B. Hinz,et al.  Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. , 2001, Molecular biology of the cell.

[56]  Shu Chien,et al.  A Strain Device Imposing Dynamic and Uniform Equi-Biaxial Strain to Cultured Cells , 1998, Annals of Biomedical Engineering.

[57]  R. Lal,et al.  Hemodynamics and Atherogenesis , 1994 .

[58]  D. Ingber,et al.  Mechanical behavior in living cells consistent with the tensegrity model , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[59]  I. Weissman,et al.  Stem cells, cancer, and cancer stem cells , 2001, Nature.

[60]  B. H. Campbell,et al.  TGF-β1, TGF-β3, and PGE2 regulate contraction of human patellar tendon fibroblasts , 2004 .

[61]  F. Grandi,et al.  Single molecule force spectroscopy discovers mechanochemical switches in biology: The case of the disulfide bond , 2006 .

[62]  G. Gabbiani,et al.  Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors. , 2001, Journal of cell science.

[63]  A. Mata,et al.  Analysis of Connective Tissue Progenitor Cell Behavior on Polydimethylsiloxane Smooth and Channel Micro-Textures , 2002, Biomedical microdevices.

[64]  Stuart B Goodman,et al.  Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta3-induced chondrogenesis by adult human mesenchymal stem cells in vitro. , 2006, Tissue engineering.

[65]  Antonella Farsetti,et al.  Epigenetic Histone Modification and Cardiovascular Lineage Programming in Mouse Embryonic Stem Cells Exposed to Laminar Shear Stress , 2005 .

[66]  S. Dooley,et al.  Abrogation of Transforming Growth Factor-β Signaling by SMAD7 Inhibits Collagen Gel Contraction of Human Dermal Fibroblasts* , 2005, Journal of Biological Chemistry.

[67]  F. Berenbaum,et al.  Prostaglandin E2 synthesis in cartilage explants under compression: mPGES-1 is a mechanosensitive gene , 2006, Arthritis research & therapy.

[68]  Y. Abiko,et al.  Effect of different magnitudes of tension force on prostaglandin E2 production by human periodontal ligament cells. , 1994, Archives of oral biology.

[69]  J. Urban,et al.  The effects of hydrostatic pressure on matrix synthesis in articular cartilage , 1991, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[70]  A. Lumsden,et al.  Cyclic strain induces vascular smooth muscle cell differentiation from murine embryonic mesenchymal progenitor cells. , 2007, Surgery.

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

[72]  M. Schwartz,et al.  Integrins: emerging paradigms of signal transduction. , 1995, Annual review of cell and developmental biology.

[73]  S. Glagov,et al.  A new in vitro system for studying cell response to mechanical stimulation. Different effects of cyclic stretching and agitation on smooth muscle cell biosynthesis. , 1977, Experimental cell research.

[74]  Qizhi Yao,et al.  Shear Stress Induces Endothelial Differentiation From a Murine Embryonic Mesenchymal Progenitor Cell Line , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[75]  S. Usami,et al.  Shear Stress Increases ICAM-1 and Decreases VCAM-1 and E-selectin Expressions Induced by Tumor Necrosis Factor-&agr; in Endothelial Cells , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[76]  M. Chiquet,et al.  Mechanical signals regulating extracellular matrix gene expression in fibroblasts , 2005, Scandinavian journal of medicine & science in sports.

[77]  R Kujat,et al.  Mechanobiological conditioning of stem cells for cartilage tissue engineering. , 2006, Bio-medical materials and engineering.

[78]  Frederick Grinnell,et al.  Fibroblasts, myofibroblasts, and wound contraction , 1994, The Journal of cell biology.

[79]  H. Schnaper,et al.  Sp1 and Smad Proteins Cooperate to Mediate Transforming Growth Factor-β1-induced α2(I) Collagen Expression in Human Glomerular Mesangial Cells* , 2001, The Journal of Biological Chemistry.

[80]  T D Brown,et al.  Techniques for mechanical stimulation of cells in vitro: a review. , 2000, Journal of biomechanics.

[81]  S. Woo,et al.  Tissue engineering of ligament and tendon healing. , 1999, Clinical orthopaedics and related research.

[82]  T. Young,et al.  Effects of Cyclic Mechanical Stretching on the mRNA Expression of Tendon/Ligament-Related and Osteoblast-Specific Genes in Human Mesenchymal Stem Cells , 2008, Connective tissue research.

[83]  G. Laurent,et al.  Mechanical load enhances procollagen processing in dermal fibroblasts by regulating levels of procollagen C-proteinase. , 1999, Experimental cell research.

[84]  A. Desmoulière,et al.  Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts , 1993, The Journal of cell biology.

[85]  Kenneth M. Yamada,et al.  Transmembrane crosstalk between the extracellular matrix and the cytoskeleton , 2001, Nature Reviews Molecular Cell Biology.

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

[87]  M. Glogauer,et al.  Regulation of stretch-activated intracellular calcium transients by actin filaments. , 1999, Biochemical and biophysical research communications.

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

[89]  C. Simmons,et al.  Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal-regulated kinase (ERK1/2) signaling pathway. , 2003, Journal of biomechanics.

[90]  Albert K. Harris,et al.  Fibroblast traction as a mechanism for collagen morphogenesis , 1981, Nature.

[91]  K. Cunningham,et al.  The role of shear stress in the pathogenesis of atherosclerosis , 2005, Laboratory Investigation.

[92]  P. Janmey,et al.  The specific NH2-terminal sequence Ac-EEED of alpha-smooth muscle actin plays a role in polymerization in vitro and in vivo , 1995, The Journal of cell biology.

[93]  D. Bigner,et al.  SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility. , 2004, Molecular cancer therapeutics.

[94]  David A. Schultz,et al.  A mechanosensory complex that mediates the endothelial cell response to fluid shear stress , 2005, Nature.

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

[96]  Tom Shemesh,et al.  Assembly and mechanosensory function of focal adhesions: experiments and models. , 2006, European journal of cell biology.

[97]  J. Jansen,et al.  Early spreading events of fibroblasts on microgrooved substrates. , 2000, Journal of biomedical materials research.

[98]  Donald E Ingber,et al.  Micropatterning tractional forces in living cells. , 2002, Cell motility and the cytoskeleton.

[99]  Feng Xu,et al.  Assembly and reorientation of stress fibers drives morphological changes to endothelial cells exposed to shear stress. , 2004, The American journal of pathology.

[100]  B. Hinz,et al.  The N-terminal Ac-EEED sequence plays a role in α-smooth-muscle actin incorporation into stress fibers , 2005, Journal of Cell Science.

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

[102]  J. Jansen,et al.  Attachment of fibroblasts on smooth and microgrooved polystyrene. , 1999, Journal of biomedical materials research.

[103]  Jeen-Shang Lin,et al.  Cell traction force and measurement methods , 2007, Biomechanics and modeling in mechanobiology.

[104]  D. Stupack The biology of integrins. , 2007, Oncology.

[105]  H. Cheung,et al.  Temporal Expression Patterns and Corresponding Protein Inductions of Early Responsive Genes in Rabbit Bone Marrow–Derived Mesenchymal Stem Cells Under Cyclic Compressive Loading , 2005, Stem cells.

[106]  Joseph W Freeman,et al.  Collagen self-assembly and the development of tendon mechanical properties. , 2003, Journal of biomechanics.

[107]  H. Drexler,et al.  Role of endogenous bradykinin in human coronary vasomotor control. , 1995, Circulation.

[108]  David L Kaplan,et al.  Tissue engineering of ligaments. , 2004, Annual review of biomedical engineering.

[109]  D. Mooney,et al.  Engineered smooth muscle tissues: regulating cell phenotype with the scaffold. , 1999, Experimental cell research.

[110]  Song Li,et al.  Anisotropic mechanosensing by mesenchymal stem cells , 2006, Proceedings of the National Academy of Sciences.

[111]  J. Frangos,et al.  The shear stress of it all: the cell membrane and mechanochemical transduction , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[112]  M. Tammi,et al.  Expression of reduced amounts of structurally altered aggrecan in articular cartilage chondrocytes exposed to high hydrostatic pressure. , 1994, The Biochemical journal.

[113]  J. Bishop,et al.  Regulation of cardiovascular collagen synthesis by mechanical load. , 1999, Cardiovascular research.

[114]  G. Gabbiani,et al.  Mechanisms of myofibroblast activity and phenotypic modulation. , 1999, Experimental cell research.

[115]  D R Carter,et al.  Time-dependent effects of intermittent hydrostatic pressure on articular chondrocyte type II collagen and aggrecan mRNA expression. , 2000, Journal of rehabilitation research and development.

[116]  A Ratcliffe,et al.  The effects of matrix compression on proteoglycan metabolism in articular cartilage explants. , 1994, Osteoarthritis and cartilage.

[117]  Jeen-Shang Lin,et al.  Mechanoregulation of gene expression in fibroblasts. , 2007, Gene.

[118]  Shu Chien,et al.  Molecular basis of mechanical modulation of endothelial cell migration. , 2005, Frontiers in bioscience : a journal and virtual library.

[119]  Michael P. Sheetz,et al.  Force transduction by Triton cytoskeletons , 2002, The Journal of cell biology.

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

[121]  Zuisei Kanno,et al.  Effects of mechanical strain on proliferation and differentiation of bone marrow stromal cell line ST2 , 2004, Journal of Bone and Mineral Metabolism.

[122]  Richard T. Lee,et al.  Cell mechanics and mechanotransduction: pathways, probes, and physiology. , 2004, American journal of physiology. Cell physiology.

[123]  Bernadette Ateghang,et al.  Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain‐induced cardiovascular differentiation , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[124]  D. Scadden,et al.  The stem-cell niche as an entity of action , 2006, Nature.

[125]  Jeen-Shang Lin,et al.  Determining substrate displacement and cell traction fields--a new approach. , 2006, Journal of theoretical biology.

[126]  Michael H Hsieh,et al.  Molecular mechanism of apoptosis induced by mechanical forces. , 2005, International review of cytology.

[127]  D. Taylor,et al.  Keratocytes generate traction forces in two phases. , 1999, Molecular biology of the cell.

[128]  Timothy J. Mitchison,et al.  Identification of Novel Graded Polarity Actin Filament Bundles in Locomoting Heart Fibroblasts: Implications for the Generation of Motile Force , 1997, The Journal of cell biology.

[129]  B. L. Langille,et al.  Shear-induced reorganization of endothelial cell cytoskeleton and adhesion complexes. , 2004, Trends in cardiovascular medicine.

[130]  J. Stull,et al.  Dedicated Myosin Light Chain Kinases with Diverse Cellular Functions* , 2001, The Journal of Biological Chemistry.

[131]  A. Geinoz,et al.  The Fibronectin Domain ED-A Is Crucial for Myofibroblastic Phenotype Induction by Transforming Growth Factor-β1 , 1998, Journal of Cell Biology.

[132]  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.

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

[134]  B L Langille,et al.  Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[135]  T Delhaas,et al.  An equibiaxial strain system for cultured cells. , 1996, The American journal of physiology.

[136]  F. Beier,et al.  RhoA/ROCK Signaling Regulates Chondrogenesis in a Context-dependent Manner* , 2006, Journal of Biological Chemistry.

[137]  Ben Fabry,et al.  Traction fields, moments, and strain energy that cells exert on their surroundings. , 2002, American journal of physiology. Cell physiology.

[138]  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.

[139]  F. Barry,et al.  Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. , 2001, Experimental cell research.

[140]  A. Grodzinsky,et al.  Kinetics of the chondrocyte biosynthetic response to compressive load and release. , 1989, Biochimica et biophysica acta.

[141]  C Zhu,et al.  Cell mechanics: mechanical response, cell adhesion, and molecular deformation. , 2000, Annual review of biomedical engineering.

[142]  F Guilak,et al.  Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. , 2002, Osteoarthritis and cartilage.

[143]  K. Cunningham,et al.  The role of shear stress in the pathogenesis of atherosclerosis , 2005, Laboratory Investigation.

[144]  Yubo Sun,et al.  Effects of Cyclic Compressive Loading on Chondrogenesis of Rabbit Bone‐Marrow Derived Mesenchymal Stem Cells , 2004, Stem cells.

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

[146]  P. Lelkes,et al.  Gene expression profiling of vascular endothelial cells exposed to fluid mechanical forces: relevance for focal susceptibility to atherosclerosis. , 2004, Endothelium : journal of endothelial cell research.

[147]  K. Moore,et al.  Stem Cells and Their Niches , 2006, Science.

[148]  Natalia Juncosa-Melvin,et al.  Effects of mechanical stimulation on the biomechanics and histology of stem cell-collagen sponge constructs for rabbit patellar tendon repair. , 2006, Tissue engineering.

[149]  F. Gabbiani,et al.  Action of general and alpha-smooth muscle-specific actin antibody microinjection on stress fibers of cultured smooth muscle cells. , 1990, Experimental cell research.

[150]  M. Kurabayashi,et al.  Basic Fibroblast Growth Factor Antagonizes Transforming Growth Factor-β1–Induced Smooth Muscle Gene Expression Through Extracellular Signal–Regulated Kinase 1/2 Signaling Pathway Activation , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[151]  Viola Vogel,et al.  Mechanotransduction involving multimodular proteins: converting force into biochemical signals. , 2006, Annual review of biophysics and biomolecular structure.

[152]  K. Burridge,et al.  Focal adhesions, contractility, and signaling. , 1996, Annual review of cell and developmental biology.

[153]  M. Dembo,et al.  Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts. , 2001, Biophysical journal.

[154]  K. Naruse,et al.  Uni‐axial cyclic stretch induces the activation of transcription factor nuclear factor κB in human fibroblast cells , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

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

[156]  F. Silver,et al.  Mechanosensing and mechanochemical transduction: how is mechanical energy sensed and converted into chemical energy in an extracellular matrix? , 2003, Critical reviews in biomedical engineering.

[157]  Viola Vogel,et al.  Force-Induced Unfolding of Fibronectin in the Extracellular Matrix of Living Cells , 2007, PLoS biology.

[158]  H. Rosenfeldt,et al.  Fibroblast Quiescence and the Disruption of ERK Signaling in Mechanically Unloaded Collagen Matrices* , 2000, The Journal of Biological Chemistry.

[159]  F. Beier,et al.  RhoA/ROCK Signaling Regulates Sox9 Expression and Actin Organization during Chondrogenesis* , 2005, Journal of Biological Chemistry.

[160]  Natalia Juncosa-Melvin,et al.  Mechanical stimulation increases collagen type I and collagen type III gene expression of stem cell-collagen sponge constructs for patellar tendon repair. , 2007, Tissue engineering.

[161]  Wei Chen,et al.  Endothelial mechanotransduction, nitric oxide and vascular inflammation , 2006, Journal of internal medicine.

[162]  James H.-C. Wang,et al.  Controlling Cell Responses to Cyclic Mechanical Stretching , 2005, Annals of Biomedical Engineering.

[163]  H. Vandenburgh Mechanical forces and their second messengers in stimulating cell growth in vitro. , 1992, The American journal of physiology.

[164]  Y. Castier,et al.  Molecular mechanisms of the vascular responses to haemodynamic forces , 2006 .

[165]  G. Beaupré,et al.  Hydrostatic Pressure Enhances Chondrogenic Differentiation of Human Bone Marrow Stromal Cells in Osteochondrogenic Medium , 2008, Annals of Biomedical Engineering.

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

[167]  B. Sumpio,et al.  Molecular and biological effects of hemodynamics on vascular cells. , 2004, Frontiers in bioscience : a journal and virtual library.

[168]  C. Heldin,et al.  Smad regulation in TGF-beta signal transduction. , 2001, Journal of cell science.

[169]  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.

[170]  D. Ingber Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. , 2002, Circulation research.

[171]  A. Harris,et al.  Silicone rubber substrata: a new wrinkle in the study of cell locomotion. , 1980, Science.

[172]  K. Jacobson,et al.  Traction forces generated by locomoting keratocytes , 1994, The Journal of cell biology.

[173]  Li-chi Han,et al.  Mechanical strain induces osteogenic differentiation: Cbfa1 and Ets-1 expression in stretched rat mesenchymal stem cells. , 2008, International journal of oral and maxillofacial surgery.

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

[175]  C Krettek,et al.  Effects of cyclic longitudinal mechanical strain and dexamethasone on osteogenic differentiation of human bone marrow stromal cells. , 2004, European cells & materials.

[176]  M. Glucksberg,et al.  Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer , 2006, Gene Therapy.

[177]  G. Vunjak‐Novakovic,et al.  Stem cell-based tissue engineering with silk biomaterials. , 2006, Biomaterials.

[178]  K. Moriyama,et al.  Interferon‐γ inhibits the myofibroblastic phenotype of rat palatal fibroblasts induced by transforming growth factor‐β1 in vitro , 1999 .

[179]  Jean-Jacques Meister,et al.  Focal adhesion size controls tension-dependent recruitment of α-smooth muscle actin to stress fibers , 2006, The Journal of cell biology.

[180]  C. McCulloch,et al.  Multiple roles of α-smooth muscle actin in mechanotransduction , 2006 .

[181]  J. Wang,et al.  Fibroblast responses to cyclic mechanical stretching depend on cell orientation to the stretching direction. , 2004, Journal of biomechanics.

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

[183]  K. Jepsen,et al.  Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[184]  Giulio Gabbiani,et al.  Mechanisms of force generation and transmission by myofibroblasts. , 2003, Current opinion in biotechnology.

[185]  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.

[186]  P. Angele,et al.  Cyclic, mechanical compression enhances chondrogenesis of mesenchymal progenitor cells in tissue engineering scaffolds. , 2004, Biorheology.

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

[188]  J. Wang,et al.  Repetitively Stretched Tendon Fibroblasts Produce Inflammatory Mediators , 2004, Clinical orthopaedics and related research.

[189]  G. Pfitzer highlighted topics Signal Transduction in Smooth Muscle Invited Review: Regulation of myosin phosphorylation in smooth muscle , 2022 .

[190]  Frederick Grinnell,et al.  Fibroblast biology in three-dimensional collagen matrices. , 2003, Trends in cell biology.

[191]  B. H. Campbell,et al.  Cyclic Mechanical Stretching of Human Tendon Fibroblasts Increases the Production of Prostaglandin E 2 and Levels of Cyclooxygenase Expression: A Novel In Vitro Model Study , 2003, Connective tissue research.

[192]  John A. Frangos,et al.  G protein-coupled receptors sense fluid shear stress in endothelial cells , 2006, Proceedings of the National Academy of Sciences.

[193]  M. Sheetz,et al.  A micromachined device provides a new bend on fibroblast traction forces. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[194]  C. McCulloch,et al.  Dependence of collagen remodelling on α‐smooth muscle actin expression by fibroblasts , 1994 .

[195]  M. Daemen,et al.  Collagen remodeling after myocardial infarction in the rat heart. , 1995, The American journal of pathology.

[196]  R. Silver,et al.  Contractile activity and smooth muscle alpha-actin organization in thrombin-induced human lung myofibroblasts. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[197]  A. Banes,et al.  Culturing cells in a mechanically active environment. , 1990, American biotechnology laboratory.

[198]  J. Jansen,et al.  The effect of combined cyclic mechanical stretching and microgrooved surface topography on the behavior of fibroblasts. , 2005, Journal of biomedical materials research. Part A.

[199]  Toshihiro Akaike,et al.  Gene expression of type I and type III collagen by mechanical stretch in anterior cruciate ligament cells. , 2002, Cell structure and function.

[200]  M. Yost,et al.  Influence of the extracellular matrix on the regulation of cardiac fibroblast behavior by mechanical stretch , 2004, Journal of cellular physiology.

[201]  J. Holtz,et al.  Shear stress-dependent expression of apoptosis-regulating genes in endothelial cells. , 2000, Biochemical and biophysical research communications.

[202]  D. Brunette,et al.  Substratum surface topography alters cell shape and regulates fibronectin mRNA level, mRNA stability, secretion and assembly in human fibroblasts. , 1995, Journal of cell science.

[203]  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.

[204]  Savio L-Y Woo,et al.  Cell orientation determines the alignment of cell-produced collagenous matrix. , 2003, Journal of biomechanics.

[205]  G. Gabbiani,et al.  The myofibroblast in wound healing and fibrocontractive diseases , 2003, The Journal of pathology.

[206]  B. Li,et al.  Development of micropost force sensor array with culture experiments for determination of cell traction forces. , 2007, Cell motility and the cytoskeleton.

[207]  C F Dewey,et al.  Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[208]  C. Frank,et al.  Natural history of healing in the repaired medial collateral ligament , 1983, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[209]  Y. Abiko,et al.  Induction of COX-2 expression by mechanical tension force in human periodontal ligament cells. , 1998, Journal of periodontology.

[210]  M. Sheetz,et al.  Local force and geometry sensing regulate cell functions , 2006, Nature Reviews Molecular Cell Biology.

[211]  N. Tamura,et al.  Shear stress augments expression of C-type natriuretic peptide and adrenomedullin. , 1997, Hypertension.

[212]  R. Chambers,et al.  Activation of Fibroblast Procollagen α1(I) Transcription by Mechanical Strain Is Transforming Growth Factor-β-dependent and Involves Increased Binding of CCAAT-binding Factor (CBF/NF-Y) at the Proximal Promoter* , 2002, The Journal of Biological Chemistry.

[213]  David A Lee,et al.  Dynamic compressive strain influences chondrogenic gene expression in human mesenchymal stem cells. , 2006, Biorheology.

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

[215]  T. Leung,et al.  Rho-mediated assembly of stress fibers is differentially regulated in corneal fibroblasts and myofibroblasts. , 2003, Experimental cell research.

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

[217]  R. D. du Bois,et al.  Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. , 1997, The American journal of pathology.

[218]  B. Moran,et al.  A system to impose prescribed homogenous strains on cultured cells. , 2001, Journal of applied physiology.

[219]  D. Ingber,et al.  Mechanotransduction: All Signals Point to Cytoskeleton, Matrix, and Integrins , 2002, Science's STKE.

[220]  E. Capriotti,et al.  Hierarchical Mechanochemical Switches in Angiostatin , 2006, Chembiochem : a European journal of chemical biology.

[221]  M. Greenberg,et al.  Stimulation of growth factor receptor signal transduction by activation of voltage-sensitive calcium channels. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

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

[223]  Takayuki Kato,et al.  Cooperation between mDia1 and ROCK in Rho-induced actin reorganization , 1999, Nature Cell Biology.

[224]  T. Thatcher,et al.  PPARγ agonists inhibit TGF-β induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis , 2005 .

[225]  J. Ando,et al.  Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor beta. , 2008, Journal of applied physiology.

[226]  Christopher S. Chen,et al.  Cells lying on a bed of microneedles: An approach to isolate mechanical force , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[227]  S. Rennard,et al.  Smad3 mediates TGF-beta1-induced collagen gel contraction by human lung fibroblasts. , 2006, Biochemical and biophysical research communications.

[228]  M. Kurosaka,et al.  Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor‐β1 , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[229]  Elizabeth G Loboa,et al.  Differential effects on messenger ribonucleic acid expression by bone marrow-derived human mesenchymal stem cells seeded in agarose constructs due to ramped and steady applications of cyclic hydrostatic pressure. , 2007, Tissue engineering.