Collagen pp 249-267 | Cite as

Mechanical Adaptation and Tissue Remodeling

  • M. Kjær
  • S.P. Magnusson


The adaptive response of connective tissue to mechanical loading includes an increased synthesis and turnover of matrix proteins, including the collagen. Collagen formation and degradation increases with acute loading of tendon and skeletal muscle, in vivo. This increased activity is associated with local and systemic release of growth factors (e.g., IGF-1, TGF-beta, IL-6) that is temporally coupled with a rise in procollagen expression. Chronic loading of tissue, such as with physical training, will lead to increased collagen turnover and a net collagen synthesis which are together associated with a modification of the mechanical properties, including a reduction in tendon stress. Altogether this likely yields a more load-resistant tissue. The adaptation time to chronic loading is longer in tendon tissue compared to contractile elements of skeletal muscle or heart, and it is only with very prolonged loading that significant changes in gross dimensions of the tendon can be observed. Current observations support the notion that mechanical loading leads to collagen-rich tissue adaptation, and that this requires an intimate interplay between mechanical signaling and biochemical changes in the matrix, such that chemical changes can be converted into adaptations in morphology, structure and material properties.


Satellite Cell Achilles Tendon Collagen Synthesis Connective Tissue Growth Factor Eccentric Exercise 
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  1. Abrahamsson SO (1997). Similar effect of recombinant human insulin-like growth factor-I and II in cellular activities in flexor tendons of young rabbits: experimental studies in vitro. J Orthop Res 15: 256–262.CrossRefGoogle Scholar
  2. Alexander RM & Bennet-Clark HC (1977). Storage of elastic strain energy in muscle and other tissues. Nature 265: 114–117.CrossRefGoogle Scholar
  3. Almekinders LC, Vellema JH, & Weinhold PS (2002). Strain patterns in the patellar tendon and the implications for patellar tendinopathy. Knee Surg Sports Traumatol Arthrosc 10: 2–5.CrossRefGoogle Scholar
  4. Arndt AN, Bruggemann GP, Koebke J, & Segesser B (1999). Asymmetrical loading of the human triceps surae: I. Mediolateral force difference in the Achilles tendon. Foot Ankle Int 20:445–449.Google Scholar
  5. Arnoczky SP, Lavagnino M, Whallon JH, & Hoonjan A (2002). In situ cell nucleus deformation in tendons under tensile load; a morphological analysis using confocal laser microscopy. J Orthop Res 20: 29–35.CrossRefGoogle Scholar
  6. Babraj J, Cuthbertson D, Smith J, Langberg H, Miller BF, Krogsgaard M, Kjær M, & Rennie MJ (2005). Collagen synthesis in human musculoskeletal tissues and skin. Am J Physiol 99: 986–994.CrossRefGoogle Scholar
  7. Basso O, Amis AA, Race A, & Johnson DP (2002). Patellar tendon fiber strains: their differential responses to quadriceps tension. Clin Orthop 400: 246–253.CrossRefGoogle Scholar
  8. Biewener AA & Roberts TJ (2000). Muscle and tendon contributions to force, work, and elastic energy savings: a comparative perspective. Exerc Sport Sci Rev 28: 99–107.Google Scholar
  9. Birch HL, McLaughlin L, Smith RK, & Goodship AE (1999). Treadmill exercise-induced tendon hypertrophy: assessment of tendons with different mechanical functions. Equine Vet J Suppl 30: 222–226.Google Scholar
  10. Bojsen-Moller J, Hansen P, Aagaard P, Svantesson U, Kjær M, & Magnusson SP (2004). Differential displacement of the human soleus and medial gastrocnemius aponeuroses during isometric plantar flexor contractions in vivo. J Appl Physiol 97: 1908–1914.CrossRefGoogle Scholar
  11. Bojsen-Moller J, Kalliokoski KK, Seppanen M, Kjær M, & Magnusson SP (2006). Low-intensity tensile loading increases intratendinous glucose uptake in the Achilles tendon. J Appl Physiol 101: 196–201.CrossRefGoogle Scholar
  12. Buchanan CI & Marsh RL (2001). Effects of long-term exercise on the biomechanical properties of the Achilles tendon of guinea fowl. J Appl Physiol 90: 164–171.Google Scholar
  13. Chong, AK, et al. (2007). Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit Achilles tendon model. J Bone Joint Surg Am, 89: 74–81.CrossRefGoogle Scholar
  14. Crameri R, Langberg H, Jensen CH, Teisner B, Schrøder HD, & Kjær M (2004a). Activation of satellite cells in human skeletal muscle after a single bout of exercise. J Physiol 558:333–340.CrossRefGoogle Scholar
  15. Crameri R, Langberg H, Teisner B, Magnusson P, Olesen JL, Koskinen S, Suetta C, & Kjær M (2004b). Synchronous disruption of the extracellular matrix and mechanical tenderness in skeletal muscle after a single bout of eccentric loading in humans. Matrix Biol 23:259–264.CrossRefGoogle Scholar
  16. Crameri R, Aaagaard P, Qvortrup K, Langberg H, Olesen JL, & Kjær M (2007). Myofibre damage in human skeletal muscle: Effects of electrical stimulation vs voluntary contraction. J Physiol 583: 365–380.CrossRefGoogle Scholar
  17. Cresswell AG, Loscher WN, & Thorstensson A (1995). Influence of gastrocnemius muscle length on triceps surae torque development and electromyographic activity in man. Exp Brain Res 105: 283–290.CrossRefGoogle Scholar
  18. DeBoer J, Selby A, Atherton P, Smith K, Seynnes OR, Maganaris CN, Maffulli N, Movin T, Narici MV, & Rennie MJ (2007). The temporal response of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse. J Physiol 585: 241–251.CrossRefGoogle Scholar
  19. DeMos, M et al. (2007). Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study. BMC Musculoskelet Disord, 8: 16–22.CrossRefGoogle Scholar
  20. Døssing S & Kjær M (2005). Growth hormone and connective tissue in exercise. Scand. J Med Sci Sports 15: 202–210.CrossRefGoogle Scholar
  21. Finni T, Hodgson JA, Lai AM, Edgerton VR, & Sinha S (2003). Nonuniform strain of human soleus aponeurosis-tendon complex during submaximal voluntary contractions in vivo. J Appl Physiol 95: 829–837.Google Scholar
  22. Fukashiro S, Itoh M, Ichinose Y, Kawakami Y, & Fukunaga T (1995). Ultrasonography gives directly but noninvasively elastic characteristic of human tendon in vivo. Eur J Appl Physiol 71: 555–557.CrossRefGoogle Scholar
  23. Goldspink G (2006). Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting. Int J Biochem Cell Biol 38: 481–489.CrossRefGoogle Scholar
  24. Hansen P, Aagaard P, Kjær M, Larsson B, & Magnusson SP (2003). The effect of habitual running on human Achilles tendon load-deformation properties and cross-sectional area. J Appl Physiol 95: 2375–2380.Google Scholar
  25. Hansen P, Bojsen-Moller J, Aagaard P, Kjær M, & Magnusson SP (2006). Mechanical properties of the human patellar tendon, in vivo. Clin Biomech 21: 54–58.CrossRefGoogle Scholar
  26. Haraldsson BT, Aagaard P, Krogsgaard M, Alkjaer T, Kjær M, & Magnusson SP (2005). Region-specific mechanical properties of the human patella tendon. J Appl Physiol 98: 1006–1012.CrossRefGoogle Scholar
  27. Haraldsson BT, Aagard P, Qvortrup K, Bojsen-Moller J, Krogsgaard M, Koskinen S, Kjaer M, Magnusson SP (2008). Lateral force transmission between human tendon fascicles. Matrix Biol. 27:86–95.CrossRefGoogle Scholar
  28. Heinemeier K, Langberg H, Olesen JL, & Kjær M (2003) Role of transforming growth factor beta in relation to exercise induced type I collagen synthesis in human tendinous tissue. J Appl Physiol 95: 2390–2397.Google Scholar
  29. Heinemeier KM, Olesen JL, Schjerling P, Haddad F, Langberg H, Baldwin KM, & Kjær M (2007a). Short term strength training and the expression of myostatin- and IGF-I isoforms in rat muscle and tendon: Differential effects of specific contraction types. J Appl Physiol 102: 573–581.CrossRefGoogle Scholar
  30. Heinemeier KM, Olesen JL, Haddad F, Langberg H, Kjær M, Baldwin KM, & Schjerling P (2007b). Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types. J Physiol 582: 1303–1316.CrossRefGoogle Scholar
  31. Huijing PA & Jaspers RT (2005). Adaptation of muscle size and myofascial force transmission: a review and some new experimental results. Scand J Med Sci Sports 15: 349–380.CrossRefGoogle Scholar
  32. Johnson DP, Wakeley CJ, & Watt I (1996). Magnetic resonance imaging of patellar tendonitis. J Bone Joint Surg – Br 78: 452–457.Google Scholar
  33. Kadi F, Charifi N, Denis C, Lexell J, Andersern JL, Schjerling P, Olsen S, & Kjær M (2005). The behaviour of satellite cells in response to exercise: What have we learned from human studies? Pfügers Arch 451: 319–327.CrossRefGoogle Scholar
  34. Kajikawa, Y et al. (2007). GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing. J Cell Physiol 210: 684–691.CrossRefGoogle Scholar
  35. Kannus P & Jozsa L (1991). Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg [Am] 73: 1507–1525.Google Scholar
  36. Kastelic J, Galeski A, & Baer E (1978). The multicomposite structure of tendon. Connect Tissue Res 6: 11–23.CrossRefGoogle Scholar
  37. Kjær M (2004). Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 84: 649–698.CrossRefGoogle Scholar
  38. Kongsgaard M, Aagaard P, Kjær M, & Magnusson SP (2005). Structural Achilles tendon properties in athletes subjected to different exercise modes and in Achilles tendon rupture patients. J Appl Physiol 99: 1965–1971.CrossRefGoogle Scholar
  39. Kongsgaard M, Reitelseder S, Pedersen TG, Holm L, Aagaard P, Kjær M, & Magnusson SP (2007). Region specific patellar tendon hypertrophy in humans following resistance training. Acta Physiol 191: 111–112.CrossRefGoogle Scholar
  40. Koskinen SO, Heinemeier KM, Olesen JL, Langberg H, & Kjær M (2004). Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon related connective tissue. J Appl Physiol 96: 861–864.CrossRefGoogle Scholar
  41. Kovanen V (1989). Effects of ageing and physical training on rat skeletal muscle. Acta Physiol Scand 135 suppl 577: 1–56.Google Scholar
  42. Kurtz CA, Loebig TG, Anderson DD, Demeo PJ & Cambell PG (1999). Insulin-like growth factor I accelerates functional recovery from Achilles tendon injury in a rat model. Am J Sports Med 27: 363–369.Google Scholar
  43. Langberg H, Skovgaard D, Bülow J, & Kjær M (2000). Time pattern of exercise-induced changes in type-I collagen turnover after prolonged endurance exercise in humans. Calcif Tissue Int 67: 41–44.CrossRefGoogle Scholar
  44. Langberg, H., Rosendal L, & Kjær M (2001). Training induced changes in peritendinous type I collagen turnover determined by microdialysis in humans. J Physiol 534:297–302.CrossRefGoogle Scholar
  45. Langberg H, Ellingsgaard H, Madsen T, Jansson J, Magnusson SP, Aagaard P, & Kjær M (2007). Eccentric rehabilitation exercise increases peritendinous type I collagen synthesis in humans with Achilles tendinosis. Scand J Med Sci Sports 17: 61–66.Google Scholar
  46. Langberg H, Skovgaard D, Petersen LJ, Bulow J, & Kjær M (1999). Type I collagen synthesis and degradation in peritendinous tissue after exercise determined by microdialysis in humans. J Physiol 521 Pt 1: 299–306.Google Scholar
  47. Lange, KH, Andersen JL, Beyer N, Isaksson F, Larsson B, Rasmussen MH, Juul A, Bülow J, & Kjær M (2002). GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. J Clin Endocrinol Metab 87: 513–523.CrossRefGoogle Scholar
  48. Laurent GJ (1987). Dynamic state of collagen pathways of collagen degradation in vivo and their possible role in regulation of collagen mass. Am J Physiol 252: C1–C9.Google Scholar
  49. Leask A, Holmes A, & Abraham DJ (2002). Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis. Curr Rheumatol Rep 4: 136–142.CrossRefGoogle Scholar
  50. Lindahl GE, Chambers RC, Papakrivopoulou J, Dawson SJ, Jacobsen MC, Bishop JE, & Laurent GJ (2002). Activation of fibroblast procollagen alpha I(I) transcription by mechanical strain is transforming growth factor beta dependent and involves increased binding of CCAAT-binding factor (CBF/NF-y) at the proximal promotor. J Biol Chem 277: 6153–6161.CrossRefGoogle Scholar
  51. Liu SH, Shaikh R, Panossian V, Yang RS, Nelson SD, Soleiman N, Finerman GA, & Lane JM (1996). Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament. J Orthop Res 14: 526–533.CrossRefGoogle Scholar
  52. Longobardi S, Keay N, Ehrnborg C, Cittadini A, Rosen T, Dall R, Boroujerdi MA, Bassett EE, Healy ML, Pentecost C, Wallace JD, Powrie J, Jorgensen JO, & Sacca L (2000). Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group. J Clin Endocrinol Metab 85: 1505–1512.CrossRefGoogle Scholar
  53. Maffulli N, Waterston SW, Squair J, Reaper J, & Douglas AS (1999). Changing incidence of Achilles tendon rupture in Scotland: a 15-year study. Clin J Sport Med 9: 157–160.CrossRefGoogle Scholar
  54. Maganaris CN & Paul JP (1999). In vivo human tendon mechanical properties. J Physiol (Lond) 521: 307–313.CrossRefGoogle Scholar
  55. Magnusson SP, Hansen P, Aagaard P, Brond J, Dyhre-Poulsen P, Bojsen-Moller J, & Kjær M (2003). Differential strain patterns of the human gastrocnemius aponeurosis and free tendon, in vivo. Acta Physiol Scand 177: 185–195.CrossRefGoogle Scholar
  56. Magnusson SP & Kjær M (2003). Region-specific differences in Achilles tendon cross-sectional area in runners and non-runners. Eur J Appl Physiol 90: 549–553.CrossRefGoogle Scholar
  57. Magnusson SP, Qvortrup K, Larsen JO, Rosager S, Hanson P, Aagaard P, Krogsgaard M, & Kjær M (2002). Collagen fibril size and crimp morphology in ruptured and intact Achilles tendons. Matrix Biol 21: 369–377.CrossRefGoogle Scholar
  58. Miller B, Olesen JL, Hansen M, Døssing S, Crameri R, Welling RJ, Langberg H, Flyvbjerg A, Kjær M, Babraj J, Smith K, & Rennie MJ (2005). Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise. J Physiol 567:1021–1033.CrossRefGoogle Scholar
  59. Miller B, Hansen M, Olesen JL, Flyvbjerg A, Schwarz P, Babraj JA, Smith K, Rennie MJ, & Kjær M (2006a). No effect of menstrual cycle on myofibrillar and connective tissue synthesis in contracting skeletal muscle. Am J Physiol 290: E163–E168.Google Scholar
  60. Miller BF, Hansen M, Olesen JL, Schwarz P, Babraj JA, Smith K, Rennie MJ, & Kjær M (2006b). Tendon collagen synthesis at rest and after exercise in women. J Appl Physiol 102:541–546.CrossRefGoogle Scholar
  61. Mosler E, Folkhard W, Knorzer E, Nemetschek-Gansler H, Nemetschek T, & Koch MH (1985). Stress-induced molecular rearrangement in tendon collagen. J Mol Biol 182: 589–596.CrossRefGoogle Scholar
  62. Olesen JL, Heinemeier KM, Langberg H, Magnusson SP, Kjær M, & Flyvbjerg A (2006). Expression, content and localization of IGF-1 in human Achilles tendon. Conn Tissue Res 47:200–206.CrossRefGoogle Scholar
  63. Olesen, JL, Langberg H, Heinemeier K, Flyvbjerg A, & Kjær M (2007a). Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis. J Appl Physiol 102:. 214–220.CrossRefGoogle Scholar
  64. Olesen JL, Heinemeier KM, Haddad F, Langberg H, Flyvbjerg A, Kjær M, & Baldwin KM (2007b). Expression of insulin-like growth factor I, insulin-like growth factor binding proteins, and collagen mRNA in mechanically loaded plantaris tendon. J Appl Physiol 101:183–188.CrossRefGoogle Scholar
  65. Parry DA, Barnes GR, & Craig AS (1978). A comparison of the size distribution of collagen fibrils in connective tissues as a function of age and a possible relation between fibril size distribution and mechanical properties. Proc R Soc Lond B Biol Sci 203: 305–321.CrossRefGoogle Scholar
  66. Patterson-Kane JC, Wilson AM, Firth EC, Parry DA, & Goodship AE (1997). Comparison of collagen fibril populations in the superficial digital flexor tendons of exercised and nonexercised thoroughbreds. Equine Vet J 29: 121–125 [published erratum appears in Equine Vet J 1998 Mar; 30(2):176].CrossRefGoogle Scholar
  67. Puxkandl R, Zizak I, Paris O, Keckes J, Tesch W, Bernstorff S, Purslow P, & Fratzl P (2002). Viscoelastic properties of collagen: synchrotron radiation investigations and structural model. Philos Trans R Soc Lond B Biol Sci 357: 191–197.CrossRefGoogle Scholar
  68. Redaelli A, Vesentini S, Soncini M, Vena P, Mantero S, & Montevecchi FM (2003). Possible role of decorin glycosaminoglycans in fibril to fibril force transfer in relative mature tendons – a computational study from molecular to microstructural level. J Biomech 36: 1555–1569.CrossRefGoogle Scholar
  69. Reeves ND, Maganaris CN, & Narici MV (2003). Effect of strength training on human patella tendon mechanical properties of older individuals. J Physiol 548: 971–981.CrossRefGoogle Scholar
  70. Riley, GP et al. (2002) Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol 21: 185–195.CrossRefGoogle Scholar
  71. Rosager S, Aagaard P, Dyhre-Poulsen P, Neergaard K, Kjær M, & Magnusson SP (2002). Load-displacement properties of the human triceps surae aponeurosis and tendon in runners and non-runners. Scand J Med Sci Sports 12: 90–98.CrossRefGoogle Scholar
  72. Sasaki N & Odajima S (1996). Elongation mechanism of collagen fibrils and force-strain relations of tendon at each level of structural hierarchy. J Biomech 29: 1131–1136.CrossRefGoogle Scholar
  73. Sciore P, Frank CB, & Hart DA (1998). Identification of sex hormone receptors in human and rabbit ligaments of the knee by reverse transcription-polymerase chain reaction: evidence that receptors are present in tissue from both male and female subjects. J Orthop Res 16: 604–610.CrossRefGoogle Scholar
  74. Scott JE (2003). Elasticity in extracellular matrix ’shape modules’ of tendon, cartilage, etc. A sliding proteoglycan-filament model. J Physiol 553: 335–343.CrossRefGoogle Scholar
  75. Skutek M, Van Griensven M, Zeichen J, Brauer N, & Bosch U (2001). Cyclic mechanical stretching modulates secretion pattern of growth factors in human fibroblasts. Eur J Appl Physiol 86: 48–52.CrossRefGoogle Scholar
  76. Smith, RK & Webbon PM (2005). Harnessing the stem cell for the treatment of tendon injuries: heralding a new dawn? Br J Sports Med 39: 582–584.CrossRefGoogle Scholar
  77. Street SF (1983). Lateral transmission of tension in frog myofibers: a myofibrillar network and transverse cytoskeletal connections are possible transmitters. J Cell Physiol 114: 346–364.CrossRefGoogle Scholar
  78. Sykova, E. & Jendelova P (2007). Migration, fate and in vivo imaging of adult stem cells in the CNS. Cell Death Differ 14: 1336–1342.CrossRefGoogle Scholar
  79. Thompson JI & Czernuszka JT (1995). The effect of two types of cross-linking on some mechanical properties of collagen. Biomed Mater Eng 5: 37–48.Google Scholar
  80. Vesentini S, Redaelli A, & Montevecchi FM (2005). Estimation of the binding force of the collagen molecule-decorin core protein complex in collagen fibril. J Biomech 38: 433–443.CrossRefGoogle Scholar
  81. Westh E, Kongsgaard M, Bojsen-Moller J, Aagaard P, Hansen M, Kjær M, & Magnusson SP (2007). Effect of habitual exercise on the structural and mechanical properties of human tendon, in vivo, in men and women. Scand J Med Sci Sports.Google Scholar
  82. Wilson VJ, Rattray M, Tomas CR, Moreland BH, & Schulster D (1995). Growth hormone increases IGF-I, collagen type I and collagen II gene expression in dwarf rat skeletal muscle. Mol Cell Endocrinol 115: 187–197.CrossRefGoogle Scholar
  83. Woo SL, Gomez MA, Woo YK, & Akeson WH (1982). Mechanical properties of tendon and ligaments. The relationship of immobilization and exercise on tissue remodeling. Biorheology 19: 397–408.Google Scholar
  84. Yu WD, Panossian V, Hatch JD, Liu SH & Finerman GA (2001). Combined effects of estrogen and progesterone on the anterior cruciate ligament. Clin Orthop 21: 268–281.Google Scholar

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  • M. Kjær
  • S.P. Magnusson

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