Intercellular mechanotransduction: cellular circuits that coordinate tissue responses to mechanical loading.

Physical forces play an important role in modulating cell function and shaping tissue structure. Mechanotransduction, the process by which cells transduce physical force-induced signals into biochemical responses, is critical for mediating adaptations to mechanical loading in connective tissues. While much is known about mechanotransduction in cells involving forces delivered through extracellular matrix proteins and integrins, there is limited understanding of how mechanical signals are propagated through the interconnected cellular networks found in tissues and organs. We propose that intercellular mechanotransduction is a critical component for achieving coordinated remodeling responses to force application in connective tissues. We examine here recent evidence on different pathways of intercellular mechanotransduction and suggest a general model for how multicellular structures respond to mechanical loading as an integrated unit.

[1]  B. Wetton,et al.  Intercellular calcium waves mediated by diffusion of inositol trisphosphate: a two-dimensional model. , 1995, The American journal of physiology.

[2]  J A Frangos,et al.  Effect of flow on prostaglandin E2 and inositol trisphosphate levels in osteoblasts. , 1991, The American journal of physiology.

[3]  B. Sheth,et al.  Junctional Complexes in the Early Mammalian Embryo , 2000, Seminars in reproductive medicine.

[4]  R. Shore,et al.  Intercellular contacts between fibroblasts in the periodontal connective tissues of the rat. , 1981, Journal of anatomy.

[5]  Donald E. Ingber,et al.  The structural and mechanical complexity of cell-growth control , 1999, Nature Cell Biology.

[6]  J. Haefliger,et al.  Hypertension increases connexin43 in a tissue-specific manner. , 1997, Circulation.

[7]  V. Everts,et al.  Junctions between fibroblasts in mouse periodontal ligament. , 1980, Journal of periodontal research.

[8]  T. Steinberg,et al.  Human Osteoblastic Cells Propagate Intercellular Calcium Signals by Two Different Mechanisms , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  T. Inagami,et al.  Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice. , 1999, The Journal of clinical investigation.

[10]  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.

[11]  T. Yamashiro,et al.  Mechanical Stimulation Induces CTGF Expression in Rat Osteocytes , 2001, Journal of dental research.

[12]  K Luby-Phelps,et al.  Viscoelastic response of fibroblasts to tension transmitted through adherens junctions. , 1997, Biophysical journal.

[13]  S. Tseng,et al.  Regulation of collagenase, stromelysin, and gelatinase B in human conjunctival and conjunctivochalasis fibroblasts by interleukin-1beta and tumor necrosis factor-alpha. , 2000, Investigative ophthalmology & visual science.

[14]  M. McKee,et al.  Role of physical forces in regulating the form and function of the periodontal ligament. , 2000, Periodontology 2000.

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

[16]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[17]  H. Baldwin,et al.  Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin. , 2001, Development.

[18]  E. R. Dirksen,et al.  Mechanical stimulation initiates intercellular Ca2+ signaling in intact tracheal epithelium maintained under normal gravity and simulated microgravity. , 1998, American journal of respiratory cell and molecular biology.

[19]  P. Ngan,et al.  Interleukin 1 beta and prostaglandin E are involved in the response of periodontal cells to mechanical stress in vivo and in vitro. , 1991, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[20]  S. Singer Intercellular communication and cell-cell adhesion. , 1992, Science.

[21]  T. Steinberg,et al.  Connexin43 Deficiency Causes Delayed Ossification, Craniofacial Abnormalities, and Osteoblast Dysfunction , 2000, The Journal of cell biology.

[22]  J. Klein-Nulend,et al.  MECHANOTRANSDUCTION IN BONE : ROLE OF THE LACUNOCANALICULAR NETWORK , 1999 .

[23]  H. Chiao,et al.  Contraction-induced cell wounding and release of fibroblast growth factor in heart. , 1995, Circulation research.

[24]  M. Varedi,et al.  Alteration in cell morphology triggers transforming growth factor-beta 1, collagenase, and tissue inhibitor of metalloproteinases-I expression in normal and hypertrophic scar fibroblasts. , 1995, The Journal of investigative dermatology.

[25]  M. Sanderson,et al.  A role for Ca(2+)-conducting ion channels in mechanically-induced signal transduction of airway epithelial cells. , 1994, Journal of cell science.

[26]  M. Glogauer,et al.  Magnetic fields applied to collagen-coated ferric oxide beads induce stretch-activated Ca2+ flux in fibroblasts. , 1995, The American journal of physiology.

[27]  T. Steinberg,et al.  Cyclic Stretch Enhances Gap Junctional Communication Between Osteoblastic Cells , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  A. Seth,et al.  Use of conditionally immortalized mouse cardiac fibroblasts to examine the effect of mechanical stretch on alpha-smooth muscle actin. , 2001, Tissue & cell.

[29]  M. Glogauer,et al.  Calcium ions and tyrosine phosphorylation interact coordinately with actin to regulate cytoprotective responses to stretching. , 1997, Journal of cell science.

[30]  M. Takeichi Morphogenetic roles of classic cadherins. , 1995, Current opinion in cell biology.

[31]  J. Ferrier,et al.  Propagation of a calcium pulse between osteoblastic cells. , 1992, Biochemical and biophysical research communications.

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

[33]  M. d’Ortho,et al.  Role of collagenase in mediating in vitro alveolar epithelial wound repair. , 1999, Journal of cell science.

[34]  A. Gerdes,et al.  Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling. , 1999, Journal of molecular and cellular cardiology.

[35]  V. Everts,et al.  Collagen degradation in the gingiva of the mouse incisor. Epithelium-connective tissue interactions. , 1981, Journal of periodontal research.

[36]  A. Palmon,et al.  Inverse dose- and time-dependent effect of basic fibroblast growth factor on the gene expression of collagen type I and matrix metalloproteinase-1 by periodontal ligament cells in culture. , 2000, Journal of periodontology.

[37]  Y. Abiko,et al.  Stimulation of prostaglandin E2 and interleukin-1beta production from old rat periodontal ligament cells subjected to mechanical stress. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[38]  C. McCulloch,et al.  Quantitation of actin polymerization in two human fibroblast sub-types responding to mechanical stretching. , 1991, Journal of cell science.

[39]  A. A. Stein,et al.  Tension-dependent collective cell movements in the early gastrula ectoderm of Xenopus laevis embryos , 2000, Development Genes and Evolution.

[40]  N. Gilula,et al.  The Gap Junction Communication Channel , 1996, Cell.

[41]  D. C. Chase,et al.  Kinetics of Cell Proliferation and Migration Associated with Orthodontically-induced Osteogenesis , 1981, Journal of dental research.

[42]  B. Gajkowska,et al.  Changes in the ultrastructure of cytoskeleton and nuclear matrix during HaCaT keratinocyte differentiation , 2001, Experimental dermatology.

[43]  T. Slaga,et al.  Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E- cadherin , 1991, The Journal of cell biology.

[44]  B. Nusgens,et al.  Pretranslational regulation of extracellular matrix macromolecules and collagenase expression in fibroblasts by mechanical forces. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[45]  C. McCulloch,et al.  Cadherins Mediate Intercellular Mechanical Signaling in Fibroblasts by Activation of Stretch-sensitive Calcium-permeable Channels* , 2001, The Journal of Biological Chemistry.

[46]  A. Shekhter Connective tissue as an integral system: role of cell-cell and cell-matrix interactions. , 1986, Connective Tissue Research.

[47]  J A Frangos,et al.  Fluid flow stimulates rapid and continuous release of nitric oxide in osteoblasts. , 1996, The American journal of physiology.

[48]  B. Nusgens,et al.  An Interleukin-1 Loop Is Induced in Human Skin Fibroblasts upon Stress Relaxation in a Three-dimensional Collagen Gel but Is Not Involved in the Up-regulation of Matrix Metalloproteinase 1* , 1998, The Journal of Biological Chemistry.