Healing Processes of the Tendon

  • Gian Nicola Bisciotti
  • Piero VolpiEmail author
Part of the Sports and Traumatology book series (SPORTS)


The biological principles on which the healing process of the tendon is based are quite different from the biological principles that regulate the muscle healing process, although some aspects may be considered as similar. Especially the last stage, namely, the remodeling and maturation phases, is very different especially regarding the temporal length that in the tendon, in respect to the muscle, is much greater. However the healing process between the tendon and the muscle will not only differ in the length time. In effect, the extrinsic and intrinsic healing mechanisms are a peculiar feature of the tendon healing that have no similarity with what occurs in the muscle during its healing process. Therefore it is of fundamental importance, especially after tendon surgical treatment, to know the biological principles that guide the healing process of the tendon.


Growth factors Angiogenesis Extrinsic healing mechanisms Intrinsic healing mechanisms 


  1. 1.
    Leadbetter WB (1995) Anti-inflammatory therapy in sport injury: the role of nonsteroidal drugs and corticosteroid injection. Clin Sports Med 14:353–410PubMedGoogle Scholar
  2. 2.
    Leadbetter WB (1995) Cell-matrix response in tendon injury. Clin Sports Med 14:353–410PubMedGoogle Scholar
  3. 3.
    Bisciotti GN (2010) Le lesioni muscolari. Calzetti e Mariucci (eds). PerugiaGoogle Scholar
  4. 4.
    Józsa LG, Kannus P (1997) Healing and regeneration of tendon. In: Human tendons: anatomy, physiology and pathology. Human Kinetics, Champaign, pp 526–554Google Scholar
  5. 5.
    Holch M, Biewener A, Thermann H, Zwipp H (1994) Non-operative treatment of acute Achilles tendon ruptures: a clinical concept and experimental results. Sport Exerc Injury 1:18–22Google Scholar
  6. 6.
    Maagaard-Mortensen NH, Skov O, Egund N (1994) Regeneration of Achilles tendon after necrosis. Acta Orthop Scand 258(Suppl):65–87Google Scholar
  7. 7.
    Minibattle ZH (1995) Treatment of Achilles tendon rupture. Non operative functional treatment. The second Congress of EFORT, Specialty day of EFFORT. Munich, July 4th 1995. Abstract book p 83Google Scholar
  8. 8.
    Houglum PA (1992) Soft tissue healing and its impact on rehabilitation. J Sport Rehab 1:19–39CrossRefGoogle Scholar
  9. 9.
    Józsa LG, Lehto M, Kannus P, Kvist M, Vieno T et al (1989) Fibronectin an laminin in Achilles tendon. Acta Orthop Scand 70:469–471CrossRefGoogle Scholar
  10. 10.
    Letho M, Józsa LG, Kvist M, Järvinen M, Bàlint BJ, Rèffy A (1990) Fibronectin in the ruptured human Achilles tendon and its paratenon. An immunoperoxidase study. Ann Chir Gynaecol 79:72–77Google Scholar
  11. 11.
    Enwemeka CS (1989) Inflammation, cellularity, and fibrillogenesis in regenerating tendon: implications for tendon rehabilitation. Phys Ther 69(10):816–825PubMedGoogle Scholar
  12. 12.
    Garret WE, Lohnes J (1990) Cellular and matrix response to mechanical injury at the myotendinous junction. In: Leadbetter WB, Buckwalter JA, Gordon SL (eds) Sport induced inflammation. AAOS, Park Ridge, pp 215–224Google Scholar
  13. 13.
    Okuda Y, Gorski JP, An KN, Amadio PC (1987) Biomechanical, histological and biochemical analyses of canine tendon. J Orthop Res 5:60–68PubMedCrossRefGoogle Scholar
  14. 14.
    Abrahamsson SO, Lundborg G, Lohmander LS (1989) Segmental variation in microstructure, matrix synthesis and cell proliferation in rabbit flexor tendon. Scand J Plast Reconstr Surg Hand Surg 23(3):191–198PubMedGoogle Scholar
  15. 15.
    Abrahamsson SO, Lundborg G, Lohmander LS (1989) Tendon healing in vivo. An experimental model. Scand J Plast Reconstr Surg Hand Surg 23(3):199–205PubMedGoogle Scholar
  16. 16.
    Dovi JV, He LK, Di Pietro LA (2003) Accelerated wound closure in neutrophil-depleted mice. J Leukoc Biol 73(4):448–455PubMedCrossRefGoogle Scholar
  17. 17.
    Godbout C, Bilodeau R, Van Rooijen N, Bouchard P, Frenette J (2010) Transient neutropenia increases macrophage accumulation and cell proliferation but does not improve repair following intratendinous rupture of Achilles tendon. J Orthop Res 28(8):1084–1091PubMedGoogle Scholar
  18. 18.
    Mirza R, Di Pietro LA, Koh TJ (2009) Selective and specific macrophage ablation is detrimental to wound healing in mice. Am J Pathol 175(6):2454–2462PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Khanna S, Biswas S, Shang Y, Collard E, Azad A, Kauh C, Bhasker V, Gordillo GM, Sen CK, Roy S (2010) Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One 5(3):e9539PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Bréchot N, Gomez E, Bignon M, Khallou-Laschet J, Dussiot M, Cazes A, Alanio-Bréchot C, Durand M, Philippe J, Silvestre JS, Van Rooijen N, Corvol P, Nicoletti A, Chazaud B, Germain S (2008) Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice. PLoS One 3(12):e3950PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Hays PL, Kawamura S, Deng XH, Dagher E, Mithoefer K, Ying L, Rodeo SA (2008) The role of macrophages in early healing of a tendon graft in a bone tunnel. J Bone Joint Surg Am 90(3):565–579PubMedCrossRefGoogle Scholar
  22. 22.
    Sercarz EE, Maverakis E (2004) Recognition and function in a degenerate immune system. Mol Immunol 40(14-15):1003–1008PubMedCrossRefGoogle Scholar
  23. 23.
    Krysko DV, D’Herde K, Vandenabeele P (2006) Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11:1709–1726PubMedCrossRefGoogle Scholar
  24. 24.
    Poon IK, Hulett MD, Parish CR (2010) Molecular mechanism of late apoptotic/necrotic cell clearance. Cell Death Differ 28:340–345Google Scholar
  25. 25.
    Woodall J Jr, Tucci M, Mishra A, Asfour A, Benghuzzi H (2008) Cellular effects of platelet rich plasmainterleukin1 release from prp treated macrophages. Biomed Sci Instrum 44:489–494PubMedGoogle Scholar
  26. 26.
    Andia I, Sanchez M, Maffulli N (2010) Tendon healing and platelet-rich plasma therapies. Expert Opin Biol Ther 10:1–12CrossRefGoogle Scholar
  27. 27.
    Scott A, Lian Ø, Roberts CR, Cook JL, Handley CJ, Bahr R, Samiric T, Ilic MZ, Parkinson J, Hart DA, Duronio V, Khan KM (2008) Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper’s knee. Scand J Med Sci Sports 18(4):427–435PubMedCrossRefGoogle Scholar
  28. 28.
    Scott A, Lian Ø, Bahr R, Hart DA, Duronio V, Khan KM (2008) Increased mast cell numbers in human patellar tendinosis: correlation with symptom duration and vascular hyperplasia. Br J Sports Med 42(9):753–757PubMedCrossRefGoogle Scholar
  29. 29.
    Del Buono A, Battery L, Denaro V, Maccauro G, Maffulli N (2011) Tendinopathy and inflammation: some truths. Int J Immunopathol Pharmacol 24(1 Suppl 2):45–50PubMedGoogle Scholar
  30. 30.
    Peacock EE, Van Winkle W (1970) Surgery and biology of wound repair. Saunders, Philadelphia, p 331424Google Scholar
  31. 31.
    Katenkamp D, Stiller D, Schulze E (1976) Ultrastructural cytology of regenerating tendon–an experimental study. Exp Pathol (Jena) 12(1):25–37Google Scholar
  32. 32.
    Gelberman RH, Vandeberg JS, Manske PR, Akeson WH (1985) The early stages of flexor tendon healing: a morphologic study of the first fourteen days. J Hand Surg Am 10(6 Pt 1):776–784PubMedCrossRefGoogle Scholar
  33. 33.
    Gelberman RH, An KA, Banes A, Goldberg V (1988) Tendon. In: Woo S, Buckwalter JA (eds) Injury and repair of the musculoskeletal soft tissue. AAOS, Ark Ridge, pp 1–40Google Scholar
  34. 34.
    Garner WL, McDonald JA, Koo M, Kuhn C 3rd, Weeks PM (1989) Identification of the collagen-producing cells in healing flexor tendons. Plast Reconstr Surg 83(5):875–879PubMedCrossRefGoogle Scholar
  35. 35.
    Chang J, Most D, Thunder R, Mehrara B, Longaker MT, Lineaweaver WC (1998) Molecular studies in flexor tendon wound healing: the role of basic fibroblast growth factor gene expression. J Hand Surg Am 23:1052–1058PubMedCrossRefGoogle Scholar
  36. 36.
    Wang JH (2006) Mechanobiology of tendon. J Biomech 39(9):1563–1582PubMedCrossRefGoogle Scholar
  37. 37.
    Bisciotti GN, Capellu M, Hidalgo J et al (2007) Comparison of stiffness resulting from different surgical methods of repair of Achilles tendon rupture. Min Ort Traum 58(2):107–114Google Scholar
  38. 38.
    Everts V, Van der Zee E, Creemers L, Beertsen W (1996) Phagocytosis and intracellular digestion of collagen, its role in turnover and remodeling. Histochem J 28:229–245PubMedCrossRefGoogle Scholar
  39. 39.
    Ackermann PW, Ahmed M, Kreicbergs A (2002) Early nerve regeneration after Achilles tendon rupture – a prerequisite for healing? A study in the rat. J Orthop Res 20:849–856PubMedCrossRefGoogle Scholar
  40. 40.
    Stayaert AE, Burssens PJ, Vercruysse CW et al (2006) The effects of substance P on the biomechanics properties of ruptured rat Achilles’ tendon. Arch Phys Med Rehabil 87:254–258CrossRefGoogle Scholar
  41. 41.
    Burssens P, Stayaert A, Forsyth R et al (2005) Exogenously administered substance P and neutral endopeptidase inhibitors stimulate fibroblast proliferation, angiogenesis, and collagen organization during Achilles tendon healing. Foot Ankle Int 26:832–839PubMedGoogle Scholar
  42. 42.
    Carlsson O, Schizas N, Li J, Ackermann PW (2011) Substance P injections enhance tissue proliferation and regulate sensory nerve ingrowth in rat tendon repair. Scand J Med Sci Sports 21(4):562–569PubMedCrossRefGoogle Scholar
  43. 43.
    Mammoto T, Seerattan RA, Paulson KD et al (2008) Nerve growth factor improves ligament healing. J Orthop Res 26:957–964PubMedCrossRefGoogle Scholar
  44. 44.
    Ivie TJ, Bray RC, Salo PT (2002) Denervation impairs healing of the rabbit medial collateral ligament. J Orthop Res 20:990–995PubMedCrossRefGoogle Scholar
  45. 45.
    Nelson L, Fairclough J, Archer CW (2010) Use of stem cells in the biological repair of articular cartilage. Expert Opin Biol Ther 10:43–55PubMedCrossRefGoogle Scholar
  46. 46.
    Lui PP, Cheuk YC, Hung LK, Fu CF (2007) Increased apoptosis at the late stage of tendon healing. Wound Repair Regen 15:702–707PubMedCrossRefGoogle Scholar
  47. 47.
    Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776PubMedCrossRefGoogle Scholar
  48. 48.
    Kaufmann SH, Hengartner MO (2001) Programmed cell death: alive and well in the new millennium. Trends Cell Biol 11:526–534PubMedCrossRefGoogle Scholar
  49. 49.
    Barkhausen T, Van Griensven M, Zeichen J, Bosch U (2003) Modulation of cell function of human tendon fibroblast by different repetitive cyclic mechanical stress patterns. Exp Toxicol Pathol 55:153–158PubMedCrossRefGoogle Scholar
  50. 50.
    Stutek M, Van Griensven M, Zeichen J, Brauer N, Bosch U (2003) Cyclic mechanical stretching of human patellar tendon fibroblast: activation of JNK and modulation of apoptosis. Knee Surg Sports Traumatol Arthrosc 11:122–129Google Scholar
  51. 51.
    Scott A, Khan KM, Herr J, Cook JL, Lian O, Duronio V (2005) Hight strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat tibialis anterior model. Br J Sports Med 39:25CrossRefGoogle Scholar
  52. 52.
    Blumenthal NC, Ricci C, Breger L, Zychlinsky A, Solomon H et al (1997) Effects of low-intensity AC and/or DC electromagnetic fields on cell attachment and induction of apoptosis. Biolectromagnetics 18:264–272CrossRefGoogle Scholar
  53. 53.
    Yuan J, Murrel GA, Trickett A, Wang MX (2003) Involvement of cytochrome c release and caspase-3 activation in the oxidative stress-induced apoptosis in human tendon fibroblast. Biochim Biophys Acta 1641:35–41PubMedCrossRefGoogle Scholar
  54. 54.
    Sendzik J, Shakibaei M, Schafer-Korting M, Stahlmann R (2005) Fluoroquinolones cause changes in extracellular matrix, signaling proteins, metalloproteinases and caspase-3 in cultured human tendon cells. Toxicology 212:24–36PubMedCrossRefGoogle Scholar
  55. 55.
    Hosaka Y, Teraoka H, Yamamoto E, Ueda H, Takehana K (2005) Mechanism of cell death in inflamed superficial digital flexor tendon in horse. J Comp Pathol 132:51–58PubMedCrossRefGoogle Scholar
  56. 56.
    Chuen FS, Chuk CY, Ping WY, Nar WW, Kim HL, Ming CK (2004) Immunohistochemical characterization of cells in adult human patellar tendon. J Histochem Cytochem 52:1151–1157PubMedCrossRefGoogle Scholar
  57. 57.
    Daugas E, Nochy D, Ravagnag L, Loeffer M et al (2000) Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett 476:118–123PubMedCrossRefGoogle Scholar
  58. 58.
    Desmouliere A (1995) Factors influencing myofibroblast differentiation during wound healing and fibrosis. Cell Biol Int 19:471–476PubMedCrossRefGoogle Scholar
  59. 59.
    Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive disease. J Pathol 200(4):500–503PubMedCrossRefGoogle Scholar
  60. 60.
    Kuroda R, Kurosaka M, Yoshiya S, Mizuno K (2000) Localization of growth factors in the reconstructed anterior cruciate ligament: immunohistological study in dogs. Knee Surg Sports Traumatol Arthrosc 8:120–126PubMedCrossRefGoogle Scholar
  61. 61.
    Visser LC, Arnoczky SP, Caballero O, Egerbacher M (2010) Platelet-rich fibrin constructs elute higher concentrations of transforming growth factor-β1 and increase tendon cell proliferation over time when compared to blood clots: a comparative in vitro analysis. Vet Surg 39(7):811–817PubMedCrossRefGoogle Scholar
  62. 62.
    Duffy FJ Jr, Seiler JG, Gelberman RH, Hergrueter CA (1995) Growth factors and canine flexor tendon healing: initial studies in uninjured and repair models. J Hand Surg Am 20:645–649PubMedCrossRefGoogle Scholar
  63. 63.
    Chang J, Most D, Stelnicki E, Siebert JW, Longaker MT, Hui K, Lineaweaver WC (1997) Gene expression of transforming growth factor beta-1 in rabbit zone II flexor tendon wound healing: evidence for dual mechanisms of repair. Plast Reconstr Surg 100:937–944PubMedCrossRefGoogle Scholar
  64. 64.
    Oryan A, Moshiri A (2011) A long term study on the role of exogenous human recombinant basic fibroblast growth factor on the superficial digital flexor tendon healing in rabbits. J Musculoskelet Neuronal Interact 11(2):185–189PubMedGoogle Scholar
  65. 65.
    Bidder M, Towler DA, Gelberman RH, Boyer MI (2000) Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon. J Orthop Res 18:247–252PubMedCrossRefGoogle Scholar
  66. 66.
    Savitskaya YA, Izaguirre A, Sierra L, Perez F, Cruz F, Villalobos E, Almazan A, Ibarra C (2011) Effect of angiogenesis-related cytokines on rotator cuff disease: the search for sensitive biomarkers of early tendon degeneration. Clin Med Insights Arthritis Musculoskelet Disord 4:43–53PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Chang SC (1994) Cartilage-derived morphogenetic proteins. J Biol Chem 269:28227–28234PubMedGoogle Scholar
  68. 68.
    Tsubone T, Moran SL, Amadio PC, Zhao C, An KN (2004) Expression of growth factors in canine flexor tendon after laceration in vivo. Ann Plast Surg 53(4):393–397PubMedCrossRefGoogle Scholar
  69. 69.
    Chen CH, Cao Y, Wu YF, Bais AJ, Gao JS, Tang JB (2008) Tendon healing in vivo: gene expression and production of multiple growth factors in early tendon healing period. J Hand Surg Am 33(10):1834–1842PubMedCrossRefGoogle Scholar
  70. 70.
    Potenza AD (1962) Tendon healing within the flexor digital sheath in the dog: an experimental study. J Bone Joint Surg Am 44:49–64PubMedGoogle Scholar
  71. 71.
    Bergljung L (1968) Vascular reactions after tendon suture and tendon transplantation. A stereo-microangiographic study on the calcaneal tendon of the rabbit. Scand J Plast Reconstr Surg Suppl 4:7–63PubMedGoogle Scholar
  72. 72.
    Takasugi H, Inoue H, Akahori O (1976) Scanning electron microscopy of repaired tendon and pseudosheat. Hand 8:228–234PubMedCrossRefGoogle Scholar
  73. 73.
    Matthews P (1979) The pathology of flexor tendon repair. Hand 11:233–242PubMedCrossRefGoogle Scholar
  74. 74.
    Mass DP, Tuel RJ (1991) Intrinsic healing of the laceration site in human superficialis flexor tendons in vitro. J Hand Surg Am 16(1):24–30PubMedCrossRefGoogle Scholar
  75. 75.
    Williams IF, Heaton A, McCullagh KG (1980) Cell morphology and collagen types in equine tendon scar. Res Vet Sci 28(3):302–310PubMedGoogle Scholar
  76. 76.
    Schneider LH (1987) Flexor tenolysis. In: Hunter JM, Schneider LH, Mackin EJ (eds) Tendon surgery in the hand. Mosby, St Louis, pp 209–215Google Scholar
  77. 77.
    Wheeldon T (1939) The use of cellophane as a permanent tendon sheat. J Bone Joint Surg 21:393–405Google Scholar
  78. 78.
    Lundborg G (1976) Experimental flexor tendon healing without adhesion formation – A new concept of tendon nutrition and intrinsic healing mechanism. Hand 8:235–238PubMedCrossRefGoogle Scholar
  79. 79.
    Lundborg G, Hansson HA, Rank F, Rydevik B (1980) Superficial repair of severed flexor tendon in synovial environment. An experimental ultrastructural study on cellular mechanism. J Hand Surg Am 5:451–461PubMedCrossRefGoogle Scholar
  80. 80.
    Manske PE, Gelberman RH, Vandeberg JS, Lesker AP (1984) Intrinsic flexor-tendon repair. A morphologic study in vivo. J Bone Joint Surg Am 66:385–396PubMedGoogle Scholar
  81. 81.
    Lindsay WK, Thomson HG (1960) Digital flexor tendons: an experimental study. Part I. The significance of each component of the flexor mechanism in tendon healing. Br J Plast Surg 12:289–316PubMedCrossRefGoogle Scholar
  82. 82.
    Gelberman RH, Vandeberg JS, Manske PR, Akesn WH (1983) Flexor tendon healing and restoration of the gliding surface. An ultrastructural study in dogs. J Bone Joint Surg Am 65:70–80PubMedGoogle Scholar
  83. 83.
    Lundborg G, Rank F (1987) Tendon healing: intrinsic mechanism. In: Hunter JM, Schneider LH, Mackin EJ (eds) Tendon surgery in the hand. Mosby, St. Louis, pp 54–60Google Scholar
  84. 84.
    Fenwick SA, Hazleman BL, Riley GP (2002) The vasculature and its role in the damaged and healing tendon. Arthritis Res 4(4):252–260PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Aspenberg P (2007) Stimulation of tendon repair: mechanical loading, GDFs and platelets. A minireview. Int Orthop 31:783–789PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Herpin A, Lelong C, Favrel P (2004) Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans. Dev Comp Immunol 28:461–485PubMedCrossRefGoogle Scholar
  87. 87.
    Storm EE, Huynh TV, Copeland NG, Jenkins NA, Kingsley DM, Lee SJ (1994) Limb alterations in brachypodism mice due to mutations in a new member of the TGF-b superfamily. Nature 368:639–642PubMedCrossRefGoogle Scholar
  88. 88.
    Storm E, Kingsley DM (1996) Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family. Development 122:3969–3979PubMedGoogle Scholar
  89. 89.
    Mikic B (2004) Multiple effects of GDF-5 deficiency on skeletal tissues: implications for therapeutic bioengineering. Ann Biomed Eng 32:466–476PubMedCrossRefGoogle Scholar
  90. 90.
    Harada M et al (2007) Developmental failure of the intra-articular ligaments in mice with absence of growth differentiation factor 5. Osteoarthritis Cartilage 15:468–474PubMedCrossRefGoogle Scholar
  91. 91.
    Wolfman NM et al (1997) Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGFbeta gene family. J Clin Invest 100:321–330PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Dines JS et al (2007) The effect of growth differentiation factor-5-coated sutures on tendon repair in a rat model. J Shoulder Elbow Surg 16:S204–S207PubMedCrossRefGoogle Scholar
  93. 93.
    Aspenberg P, Forslund C (1999) Enhanced tendon healing with GDF 5 and 6. Acta Orthop Scand 70:51–54PubMedCrossRefGoogle Scholar
  94. 94.
    Rickert M et al (2005) Adenovirus-mediated gene transfer of growth and differentiation factor-5 into tenocytes and the healing rat Achilles tendon. Connect Tissue Res 46:175–183PubMedCrossRefGoogle Scholar
  95. 95.
    Hotten GC et al (1996) Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs. Growth Factors 13:65–74PubMedCrossRefGoogle Scholar
  96. 96.
    Kakudo N, Wang YB, Miyake S, Kushida S, Kusumoto K (2007) Analysis of osteochondroinduction using growth and differentiation factor-5 in rat muscle. Life Sci 81:137–143PubMedCrossRefGoogle Scholar
  97. 97.
    Kadesch T (1993) Consequences of heteromeric interactions among helix-loop-helix proteins. Cell Growth Differ 4:49–55PubMedGoogle Scholar
  98. 98.
    Murre C et al (1989) Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58:537–544PubMedCrossRefGoogle Scholar
  99. 99.
    Brent AE, Schweitzer R, Tabin CJ (2003) A somitic compartment of tendon progenitors. Cell 113:235–248PubMedCrossRefGoogle Scholar
  100. 100.
    Cserjesi P, Brown D, Ligon KL, Lyons GE, Copeland NG, Gilbert DJ, Jenkins NA, Olson EN (1995) Scleraxis: a basic helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis. Development 121:1099–1110PubMedGoogle Scholar
  101. 101.
    Léjard V (2007) Scleraxis and NFATc regulate the expression of the pro-alpha1(I) collagen gene in tendon fibroblasts. J Biol Chem 282:17665–17675PubMedCrossRefGoogle Scholar
  102. 102.
    Murchison N et al (2007) Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons. Development 134:2697–2708PubMedCrossRefGoogle Scholar
  103. 103.
    Aslan H, Kimelman-Bleich N, Pelled G, Gazit D (2008) Molecular targets for tendon neoformation. J Clin Invest 118(2):439–444PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Qatar Orthopaedic and Sports Medicine Hospital, FIFA Center of ExcellenceDohaQatar
  2. 2.Humanitas Clinical InstituteIRCCS, RozzanoMilanItaly
  3. 3.FC Internazionale Medical staffMilanItaly

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