Operative Techniques in Orthopaedics
Volume 20, Issue 2 , Pages 110-118 , June 2010

Mediators Leading to Fibrosis—How to Measure and Control Them in Tissue Engineering

  • Xiaodong Mu, PhD

      Affiliations

    • Laboratory of Molecular Pathology, Stem Cell Research Center, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
    • Department of Orthopaedic Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, PA
  • ,
  • Ian H. Bellayr, BS

      Affiliations

    • Laboratory of Molecular Pathology, Stem Cell Research Center, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
    • Department of Bioengineering, University of Pittsburgh, School of Medicine, Pittsburgh, PA
  • ,
  • Thomas J. Walters, PhD

      Affiliations

    • United States Army Institute of Surgical Research, Fort Sam Houston, TX
  • ,
  • Yong Li, MD, PhD

      Affiliations

    • Laboratory of Molecular Pathology, Stem Cell Research Center, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
    • Department of Orthopaedic Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, PA
    • Department of Bioengineering, University of Pittsburgh, School of Medicine, Pittsburgh, PA
    • Corresponding Author InformationAddress reprint requests to Yong Li, MD, PhD, Room 101, 3343 Forbes Ave, Gold Building, Pittsburgh, PA 15213

References 

  1. Luttikhuizen DT, Harmsen MC, Van Luyn MJ. Cellular and molecular dynamics in the foreign body reaction. Tissue Eng. 2006;12:1955–1970
  2. Jones KS. Effects of biomaterial-induced inflammation on fibrosis and rejection. Semin Immunol. 2008;20:130–136
  3. Kalluri R, Sukhatme VP. Fibrosis and angiogenesis. Curr Opin Nephrol Hypertens. 2000;9:413–418
  4. Junker JP, Kratz C, Tollback A, et al. Mechanical tension stimulates the transdifferentiation of fibroblasts into myofibroblasts in human burn scars. Burns. 2008;34:942–946
  5. Sanders YY, Kumbla P, Hagood JS. Enhanced myofibroblastic differentiation and survival in Thy-1(−) lung fibroblasts. Am J Respir Cell Mol Biol. 2007;36:226–235
  6. Badid C, Vincent M, Fouque D, et al. Myofibroblast: A prognostic marker and target cell in progressive renal disease. Ren Fail. 2001;23:543–549
  7. Badid C, Mournier N, Costa AM, et al. Role of myofibroblasts during normal tissue repair and excessive scarring: Interest of their assessment in nephropathies. Histol Histopathol. 2000;15:269–280
  8. Phan SH. Biology of fibroblasts and myofibroblasts. Proc Am Thorac Soc. 2008;5:334–337
  9. Darby IA, Hewitson TD. Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol. 2007;257:143–179
  10. Li Y, Huard J. Differentiation of muscle-derived cells into myofibroblasts in injured skeletal muscle. Am J Pathol. 2002;161:895–907
  11. Li Y, Foster W, Deasy BM, et al. Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: A key event in muscle fibrogenesis. Am J Pathol. 2004;164:1007–1019
  12. Radisky DC, Kenny PA, Bissell MJ. Fibrosis and cancer: Do myofibroblasts come also from epithelial cells via EMT?. J Cell Biochem. 2007;101:830–839
  13. Ng YY, Huang TP, Yang WC, et al. Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int. 1998;54:864–876
  14. Zavadil J, Biltzer M, Liang D, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci U S A. 2001;98:6686–6691
  15. Guarino M, Tosoni A, Nebuloni M. Direct contribution of epithelium to organ fibrosis: Epithelial-mesenchymal transition. Hum Pathol. 2009;40:1365–1376
  16. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest. 2003;112:1776–1784
  17. Zeisberg EM, Tarnavski O, Zeisberg M, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 2007;13:952–961
  18. Arciniegas E, Frid MG, Douglas IS, et al. Perspectives on endothelial-to-mesenchymal transition: Potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2007;293:L1–L8
  19. Broekema M, Harmsen MC, van Luyn MJ, et al. Bone marrow-derived myofibroblasts contribute to the renal interstitial myofibroblast population and produce procollagen I after ischemia/reperfusion in rats. J Am Soc Nephrol. 2007;18:165–175
  20. Lin WR, Brittan M, Alison MR. The role of bone marrow-derived cells in fibrosis. Cells Tissues Organs. 2008;188:178–188
  21. Strieter RM, Keeley EC, Hughes MA, et al. The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of pulmonary fibrosis. J Leukoc Biol. 2009;86:1111–1118
  22. Urtasun R, Conde de la Rosa L, Nieto N. Oxidative and nitrosative stress and fibrogenic response. Clin Liver Dis. 2008;12:769–790viii
  23. Tacke F. Monocytes and macrophages as cellular targets in Liver fibrosis. Inflamm Allergy Drug Targets. 2009;8:307–318
  24. Novo E, Marra F, Zamara E, et al. Overexpression of Bcl-2 by activated human hepatic stellate cells: Resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans. Gut. 2006;55:1174–1182
  25. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210
  26. Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol. 2005;288:R345–R353
  27. Strutz F, Neilson EG. The role of lymphocytes in the progression of interstitial disease. Kidney Int Suppl. 1994;45:S106–S110
  28. Schulze PC, Lee RT. Macrophage-mediated cardiac fibrosis. Circ Res. 2004;95:552–553
  29. Hebda PA, Collins MA, Tharp MD. Mast cell and myofibroblast in wound healing. Dermatol Clin. 1993;11:685–696
  30. de Caestecker MP, Piek E, Roberts AB. Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst. 2000;92:1388–1402
  31. Bonniaud P, Margetts PJ, Ask F, et al. TGF-beta and Smad3 signaling link inflammation to chronic fibrogenesis. J Immunol. 2005;175:5390–5395
  32. Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest. 2007;117:524–529
  33. Wahl SM. Transforming growth factor beta: The good, the bad, and the ugly. J Exp Med. 1994;180:1587–1590
  34. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol. 1998;16:137–161
  35. Gauldie J, Bonniaud P, Sime P, et al. TGF-beta, Smad3 and the process of progressive fibrosis. Biochem Soc Trans. 2007;35:661–664
  36. Berk BC, Fujiwara K, Lehoux S. ECM remodeling in hypertensive heart disease. J Clin Invest. 2007;117:568–575
  37. Sung LY, Chiu HY, Chen YL, et al. Baculovirus-mediated growth factor expression in dedifferentiated chondrocytes accelerates redifferentiation: Effects of combinational transduction. Tissue Eng Part A. 2008;15:1353–1356
  38. Chen MM, Lam A, Abraham JA, et al. CTGF expression is induced by TGF-beta in cardiac fibroblasts and cardiac myocytes: A potential role in heart fibrosis. J Mol Cell Cardiol. 2000;32:1805–1819
  39. Tschumperlin DJ, Shively JD, Kikuchu T, et al. Mechanical stress triggers selective release of fibrotic mediators from bronchial epithelium. Am J Respir Cell Mol Biol. 2003;28:142–149
  40. Zhang X, Chen X, Hong Q, et al. TIMP-1 promotes age-related renal fibrosis through upregulating ICAM-1 in human TIMP-1 transgenic mice. J Gerontol A Biol Sci Med Sci. 2006;61:1130–1143
  41. Hemmann S, Graf J, Roderfeld M, et al. Expression of MMPs and TIMPs in liver fibrosis—A systematic review with special emphasis on anti-fibrotic strategies. J Hepatol. 2007;46:955–975
  42. Selman M, Ruiz V, Cabrera S, et al. TIMP-1, −2, −3, and −4 in idiopathic pulmonary fibrosis (A prevailing nondegradative lung microenvironment?). Am J Physiol Lung Cell Mol Physiol. 2000;279:L562–L574
  43. Ruiz-Ortega M, Rodriguez-Vita J, Sanchez-Lopez E, et al. TGF-beta signaling in vascular fibrosis. Cardiovasc Res. 2007;74:196–206
  44. Rosenkranz S. TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res. 2004;63:423–432
  45. Uhal BD, Kim JK, Li X, et al. Angiotensin-TGF-beta 1 crosstalk in human idiopathic pulmonary fibrosis: Autocrine mechanisms in myofibroblasts and macrophages. Curr Pharm Des. 2007;13:1247–1256
  46. Seeland U, Haeuseler C, Hinrichs R, et al. Myocardial fibrosis in transforming growth factor-beta(1) (TGF-beta(1)) transgenic mice is associated with inhibition of interstitial collagenase. Eur J Clin Invest. 2002;32:295–303
  47. Mozes MM, Bottinger EP, Jacot TA, et al. Renal expression of fibrotic matrix proteins and of transforming growth factor-beta (TGF-beta) isoforms in TGF-beta transgenic mice. J Am Soc Nephrol. 1999;10:271–280
  48. Szardening-Kirchner C, Konrad L, Hauck EW, et al. Upregulation of mRNA expression of MCP-1 by TGF-beta1 in fibroblast cells from Peyronie's disease. World J Urol. 2009;27:123–130
  49. Kaviratne M, Hesse M, Leusink M, et al. IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. J Immunol. 2004;173:4020–4029
  50. Ma LJ, Yang H, Gaspert A, et al. Transforming growth factor-beta-dependent and -independent pathways of induction of tubulointerstitial fibrosis in beta6(−/−) mice. Am J Pathol. 2003;163:1261–1273
  51. Kang DH, Johnson RJ. Vascular endothelial growth factor: A new player in the pathogenesis of renal fibrosis. Curr Opin Nephrol Hypertens. 2003;12:43–49
  52. Kisseleva T, Brenner DA. Mechanisms of fibrogenesis. Exp Biol Med (Maywood). 2008;233:109–122
  53. Suematsu M, Suzuki H, Delano FA, et al. The inflammatory aspect of the microcirculation in hypertension: Oxidative stress, leukocytes/endothelial interaction, apoptosis. Microcirculation. 2002;9:259–276
  54. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209–218
  55. Piotrowski WJ, Marczak J. Cellular sources of oxidants in the lung. Int J Occup Med Environ Health. 2000;13:369–385
  56. Kinnula VL, Fattman CL, Tan RJ, et al. Oxidative stress in pulmonary fibrosis: A possible role for redox modulatory therapy. Am J Respir Crit Care Med. 2005;172:417–422
  57. Zhao W, Chen SS, Chen Y, et al. Kidney fibrosis in hypertensive rats: Role of oxidative stress. Am J Nephrol. 2008;28:548–554
  58. Fu X, Kassim SY, Parks WC, et al. Hypochlorous acid generated by myeloperoxidase modifies adjacent tryptophan and glycine residues in the catalytic domain of matrix metalloproteinase-7 (matrilysin): An oxidative mechanism for restraining proteolytic activity during inflammation. J Biol Chem. 2003;278:28403–28409
  59. Schuppan D, Ruehi M, Somasundaram R, et al. Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis. 2001;21:351–372
  60. Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen. 2009;17:153–162
  61. Eckes B, Zweers MC, Zhang ZG, et al. Mechanical tension and integrin alpha 2 beta 1 regulate fibroblast functions. J Investig Dermatol Symp Proc. 2006;11:66–72
  62. Maher JJ, Bissell DM. Cell-matrix interactions in liver. Semin Cell Biol. 1993;4:189–201
  63. Halliday NL, Tomasek JJ. Mechanical properties of the extracellular matrix influence fibronectin fibril assembly in vitro. Exp Cell Res. 1995;217:109–117
  64. He Y, Grinnell F. Stress relaxation of fibroblasts activates a cyclic AMP signaling pathway. J Cell Biol. 1994;126:457–464
  65. Grinnell F. Fibroblast biology in three-dimensional collagen matrices. Trends Cell Biol. 2003;13:264–269
  66. Grinnell F, Zhu M, Carlson MA, et al. Release of mechanical tension triggers apoptosis of human fibroblasts in a model of regressing granulation tissue. Exp Cell Res. 1999;248:608–619
  67. Hinz B, Mastrangelo D, Iselin CE, et al. Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol. 2001;159:1009–1020
  68. Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science. 2009;324:1673–1677
  69. Hinz B, Celetta G, Tomasek JJ, et al. Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell. 2001;12:2730–2741
  70. Wipff PJ, Rifkin DB, Meister JJ, et al. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol. 2007;179:1311–1323
  71. Follonier L, Schuab S, Meister JJ, et al. Myofibroblast communication is controlled by intercellular mechanical coupling. J Cell Sci. 2008;121:3305–3316
  72. Stocum DL. Tissue restoration through regenerative biology and medicine. Adv Anat Embryol Cell Biol. 2004;176:III–VIII1-101, [back cover]
  73. Tabata Y. Biomaterial technology for tissue engineering applications. J R Soc Interface. 2009;6(suppl 3):S311–S324
  74. Nieponice A, Gilbert TW, Badylak SF. Reinforcement of esophageal anastomoses with an extracellular matrix scaffold in a canine model. Ann Thorac Surg. 2006;82:2050–2058
  75. Hamilton JA. Nondisposable materials, chronic inflammation, and adjuvant action. J Leukoc Biol. 2003;73:702–712
  76. Robitaille R, Dusseault J, Henley N, et al. Inflammatory response to peritoneal implantation of alginate-poly-l-lysine microcapsules. Biomaterials. 2005;26:4119–4127
  77. Acharya C, Hinz B, Kundu SC. The effect of lactose-conjugated silk biomaterials on the development of fibrogenic fibroblasts. Biomaterials. 2008;29:4665–4675
  78. Wells RG. The role of matrix stiffness in hepatic stellate cell activation and liver fibrosis. J Clin Gastroenterol. 2005;39(4 suppl 2):S158–S161
  79. Cushing MC, Liao JT, Jaeggli MP, et al. Material-based regulation of the myofibroblast phenotype. Biomaterials. 2007;28:3378–3387
  80. Nakatsuji S, Yamate J, Sakuma S. Macrophages, myofibroblasts, and extracellular matrix accumulation in interstitial fibrosis of chronic progressive nephropathy in aged rats. Vet Pathol. 1998;35:352–360
  81. Holness CL, Simmons DL. Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood. 1993;81:1607–1613
  82. Hiraoka A, Horiike N, Akbar SM, et al. Expression of CD163 in the liver of patients with viral hepatitis. Pathol Res Pract. 2005;201:379–384
  83. Kohalmi F, Strausz J, Egervary M, et al. [Expression of macrophage markers in childhood and adult Langerhans histiocytosis (LCH)]. Orv Hetil. 1997;138:1399–1402
  84. Arora PD, McCulloch CA. The deletion of transforming growth factor-beta-induced myofibroblasts depends on growth conditions and actin organization. Am J Pathol. 1999;155:2087–2099
  85. Ruhs S, Nass N, Somoza V, et al. Maillard reaction products enriched food extract reduce the expression of myofibroblast phenotype markers. Mol Nutr Food Res. 2007;51:488–495
  86. Kropf J, Schurek JO, Wollner A, et al. Immunological measurement of transforming growth factor-beta1 (TGF-beta1) in blood; assay development and comparison. Clin Chem. 1997;43:1965–1974
  87. Snowden N, Coupes B, Herrick A, et al. Plasma TGF beta in systemic sclerosis: A cross-sectional study. Ann Rheum Dis. 1994;53:763–767
  88. Huang XR, Chung AC, Wang XJ, et al. Mice overexpressing latent TGF-beta1 are protected against renal fibrosis in obstructive kidney disease. Am J Physiol Renal Physiol. 2008;295:F118–F127
  89. Neumann S, Kaup FJ, Beardi B. Plasma concentration of transforming growth factor-beta1 and hepatic fibrosis in dogs. Can J Vet Res. 2008;72:428–431
  90. Toomey D, Condron C, Wu QD, et al. TGF-beta1 is elevated in breast cancer tissue and regulates nitric oxide production from a number of cellular sources during hypoxia re-oxygenation injury. Br J Biomed Sci. 2001;58:177–183
  91. Hoying JB, Yin M, Diebold R, et al. Transforming growth factor beta1 enhances platelet aggregation through a non-transcriptional effect on the fibrinogen receptor. J Biol Chem. 1999;274:31008–31013
  92. Kruse JJ, Bart CI, Leer JW, et al. Detection and quantitative measurement of transforming growth factor-beta1 (TGF-beta1) gene expression using a semi-nested competitive PCR assay. Cytokines. 1999;11:179–185
  93. Ruperez M, Lorenzo O, Blanco-Colio LM, et al. Connective tissue growth factor is a mediator of angiotensin II-induced fibrosis. Circulation. 2003;108:1499–1505
  94. Abreu JG, Ketpura NI, Reversade B, et al. Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat Cell Biol. 2002;4:599–604
  95. Gressner AM, Yagmur E, Lahme B, et al. Connective tissue growth factor in serum as a new candidate test for assessment of hepatic fibrosis. Clin Chem. 2006;52:1815–1817
  96. Sato S, Nagaoka T, Hasegawa M, et al. Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: Association with extent of skin sclerosis and severity of pulmonary fibrosis. J Rheumatol. 2000;27:149–154
  97. Dziadzio M, Usinger W, Leask A, et al. N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma. QJM. 2005;98:485–492
  98. Young-Min SA, Beeton C, Laughton R, et al. Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary Raynaud's phenomenon, and in normal controls. Ann Rheum Dis. 2001;60:846–851
  99. Ko FW, Diba C, Roth M, et al. A comparison of airway and serum matrix metalloproteinase-9 activity among normal subjects, asthmatic patients, and patients with asthmatic mucus hypersecretion. Chest. 2005;127:1919–1927
  100. Soker S, Machado M, Atala A. Systems for therapeutic angiogenesis in tissue engineering. World J Urol. 2000;18:10–18
  101. Suuronen EJ, Muzakare L, Doillon CJ, et al. Promotion of angiogenesis in tissue engineering: Developing multicellular matrices with multiple capacities. Int J Artif Organs. 2006;29:1148–1157
  102. Ueno T, Nakamura T, Torimura T, et al. Angiogenic cell therapy for hepatic fibrosis. Med Mol Morphol. 2006;39:16–21
  103. Di Raimondo F, Azzaro MP, Palumbo GA, et al. Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis. Leukemia. 2001;15:976–980
  104. Simler NR, Brenchley PE, Horrocks AW, et al. Angiogenic cytokines in patients with idiopathic interstitial pneumonia. Thorax. 2004;59:581–585
  105. McColley SA, Stellmach V, Boas SR, et al. Serum vascular endothelial growth factor is elevated in cystic fibrosis and decreases with treatment of acute pulmonary exacerbation. Am J Respir Crit Care Med. 2000;161:1877–1880
  106. Richter AG, Maughan EO, Perkins GD, et al. VEGF levels in pulmonary fibrosis. Thorax. 2005;60:171
  107. Sanvisens A, Serra I, Tural C, et al. Hyaluronic acid, transforming growth factor-beta1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus co-infection. J Viral Hepat. 2009;16:513–518
  108. Wong VS, Hughes V, Trull A, et al. Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C virus infection. J Viral Hepat. 1998;5:187–192
  109. Huard J, Li Y, Fu FH. Muscle injuries and repair: Current trends in research. J Bone Joint Surg Am. 2002;84:822–832
  110. Sato K, Li Y, Foster W, et al. Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis. Muscle Nerve. 2003;28:365–372
  111. Stock UA, Vacanti JP. Tissue engineering: Current state and prospects. Annu Rev Med. 2001;52:443–451
  112. Bianco P, Robey PG. Stem cells in tissue engineering. Nature. 2001;414:118–121
  113. Bellayr IH, Li Y. Stem cells: It's good to have choices. Journal of the American College of Certified Wound Specialists. 2009;1:92–94
  114. Urish KL, Vella JB, Okada M, et al. Antioxidant levels represent a major determinant in the regenerative capacity of muscle stem cells. Mol Biol Cell. 2009;20:509–520
  115. Trounson A. New perspectives in human stem cell therapeutic research. BMC Med. 2009;7:29
  116. Quintero AJ, Wright VJ FUFH, et al. Stem cells for the treatment of skeletal muscle injury. Clin Sports Med. 2009;28:1–11
  117. Mias C, Lairez O, Trouche E, et al. Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction. Stem Cells. 2009;27:2734–2743
  118. Tenney RM, Discher DE. Stem cells, microenvironment mechanics, and growth factor activation. Curr Opin Cell Biol. 2009;21:630–635
  119. Guilak F, Cohen DM, Estes BT, et al. Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell. 2009;5:17–26
  120. Tiede S, Ernst N, Bayat A, et al. Basic fibroblast growth factor: A potential new therapeutic tool for the treatment of hypertrophic and keloid scars. Ann Anat. 2009;191:33–44
  121. Nirmalanandhan VS, Sittampalam GS. Stem cells in drug discovery, tissue engineering, and regenerative medicine: Emerging opportunities and challenges. J Biomol Screen. 2009;14:755–768
  122. Alexakis C, Partridge T, Bou-Gharios G. Implication of the satellite cell in dystrophic muscle fibrosis: A self-perpetuating mechanism of collagen overproduction. Am J Physiol Cell Physiol. 2007;293:C661–C669
  123. Chan YS, Li Y, Foster W, et al. The use of suramin, an antifibrotic agent, to improve muscle recovery after strain injury. Am J Sports Med. 2005;33:43–51
  124. Nozaki M, Li Y, Zhu J, et al. Improved muscle healing after contusion injury by the inhibitory effect of suramin on myostatin, a negative regulator of muscle growth. Am J Sports Med. 2008;36:2354–2362
  125. Foster W, Li Y, Usas A, et al. Gamma interferon as an antifibrosis agent in skeletal muscle. J Orthop Res. 2003;21:798–804
  126. Li Y, Li J, Zhu J, et al. Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Mol Ther. 2007;15:1616–1622
  127. Bedair HS, Karthikeyan T, Quintero A, et al. Angiotensin II receptor blockade administered after injury improves muscle regeneration and decreases fibrosis in normal skeletal muscle. Am J Sports Med. 2008;36:1548–1554
  128. Ruiz-Ortega M, Ruperez M, Esteban V, et al. Molecular mechanisms of angiotensin II-induced vascular injury. Curr Hypertens Rep. 2003;5:73–79
  129. Ruiz-Ortega M, Ruperez M, Esteban V, et al. Angiotensin II: A key factor in the inflammatory and fibrotic response in kidney diseases. Nephrol Dial Transplant. 2006;21:16–20
  130. Wang W, Pan H, Murray K, et al. Matrix metalloproteinase-1 promotes muscle cell migration and differentiation. Am J Pathol. 2009;174:541–549
  131. Bedair H, Liu TT, Kaar JL, et al. Matrix metalloproteinase-1 therapy improves muscle healing. J Appl Physiol. 2007;102:2338–2345
  132. Nishimura T, Nakamura K, Kishioka Y, et al. Inhibition of matrix metalloproteinases suppresses the migration of skeletal muscle cells. J Muscle Res Cell Motil. 2008;
  133. Wipff PJ, Hinz B. Myofibroblasts work best under stress. J Bodyw Mov Ther. 2009;13:121–12729:37-44
  134. Hinz B. Tissue stiffness, latent TGF-beta1 activation, and mechanical signal transduction: Implications for the pathogenesis and treatment of fibrosis. Curr Rheumatol Rep. 2009;11:120–126

PII: S1048-6666(09)00143-8

doi: 10.1053/j.oto.2009.10.003

Operative Techniques in Orthopaedics
Volume 20, Issue 2 , Pages 110-118 , June 2010