Clinical Orthopaedics and Related Research

, Volume 466, Issue 7, pp 1528–1538 | Cite as

The Basic Science of Tendinopathy

  • Yinghua Xu
  • George A. C. MurrellEmail author
Symposium: Molecular and Clinical Developments in Tendinopathy


Tendinopathy is a common clinical problem with athletes and in many occupational settings. Tendinopathy can occur in any tendon, often near its insertion or enthesis where there is an area of stress concentration, and is directly related to the volume of repetitive load to which the tendon is exposed. Recent studies indicate tendinopathy is more likely to occur in situations that increase the “dose” of load to the tendon enthesis – including increased activity, weight, advancing age, and genetic factors. The cells in tendinopathic tendon are rounder, more numerous, and show evidence of oxidative damage and more apoptosis. These cells also produce a matrix that is thicker and weaker with more water, more immature and cartilage-like matrix proteins, and less organization. There is now evidence of a population of regenerating stem cells within tendon. These studies suggest prevention of tendinopathy should be directed at reducing the volume of repetitive loads to below that which induces oxidative-induced apoptosis and cartilage-like genes. The management strategies might involve agents or cells that induce tendon stem cell proliferation, repair and restoration of matrix integrity.


Rotator Cuff Complex Regional Pain Syndrome Tendinitis Pentosidine Plantar Fasciitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Alfredson H. The chronic painful Achilles and patellar tendon: research on basic biology and treatment. Scand J Med Sci Sports. 2005;15:252–259.PubMedCrossRefGoogle Scholar
  2. 2.
    Alfredson H, Lorentzon R. Chronic tendon pain: no signs of chemical inflammation but high concentrations of the neurotransmitter glutamate. Implications for treatment? Curr Drug Targets. 2002;3:43–54.PubMedCrossRefGoogle Scholar
  3. 3.
    Alfredson H, Ohberg L. Neovascularisation in chronic painful patellar tendinosis–promising results after sclerosing neovessels outside the tendon challenge the need for surgery. Knee Surg Sports Traumatol Arthrosc. 2005;13:74–80.PubMedCrossRefGoogle Scholar
  4. 4.
    Alfredson H, Ohberg L, Forsgren S. Is vasculo-neural ingrowth the cause of pain in chronic Achilles tendinosis? An investigation using ultrasonography and colour Doppler, immunohistochemistry, and diagnostic injections. Knee Surg Sports Traumatol Arthrosc. 2003;11:334–338.PubMedCrossRefGoogle Scholar
  5. 5.
    Amour A, Knight CG, Webster A, Slocombe PM, Stephens PE, Knauper V, Docherty AJ, Murphy G. The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. FEBS Lett. 2000;473:275–279.PubMedCrossRefGoogle Scholar
  6. 6.
    Anesini C, Borda E. Modulatory effect of the adrenergic system upon fibroblast proliferation: participation of beta 3-adrenoceptors. Auton Autacoid Pharmacol. 2002;22:177–186.PubMedCrossRefGoogle Scholar
  7. 7.
    Archambault JM, Jelinsky SA, Lake SP, Hill AA, Glaser DL, Soslowsky LJ. Rat supraspinatus tendon expresses cartilage markers with overuse. J Orthop Res. 2007;25:617–624.PubMedCrossRefGoogle Scholar
  8. 8.
    Arnoczky SP, Lavagnino M, Egerbacher M. The mechanobiological aetiopathogenesis of tendinopathy: is it the over-stimulation or the under-stimulation of tendon cells? Int J Exp Pathol. 2007;88:217–226.PubMedCrossRefGoogle Scholar
  9. 9.
    Arnoczky SP, Lavagnino M, Egerbacher M, Caballero O, Gardner K. Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med. 2007;35:763–769.PubMedCrossRefGoogle Scholar
  10. 10.
    Arnoczky SP, Tiam T, Lavagnino M, Gardner K, Schuler P, Morse P. Activation of stress-activated protein kinases (SAPK) in tendon cells following cyclic strain: the effects of strain frequency, strain magnitude, and cytosolic calcium. J Orthop Res. 2002;20:947–956.PubMedCrossRefGoogle Scholar
  11. 11.
    Astrom M. Partial rupture in chronic achilles tendinopathy. A retrospective analysis of 342 cases. Acta Orthop Scand. 1998;69:404–407.PubMedCrossRefGoogle Scholar
  12. 12.
    Astrom M, Rausing A. Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings. Clinl Orthop Relat Res. 1995;316:151–164.Google Scholar
  13. 13.
    Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci. 2002;115:3719–3727.PubMedCrossRefGoogle Scholar
  14. 14.
    Bank RA, Krikken M, Beekman B, Stoop R, Maroudas A, Lafeber FP, te Koppele JM. A simplified measurement of degraded collagen in tissues: application in healthy, fibrillated and osteoarthritic cartilage. Matrix Biology. 1997;16:233–243.PubMedCrossRefGoogle Scholar
  15. 15.
    Bank RA, TeKoppele JM, Oostingh G, Hazleman BL, Riley GP. Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis. 1999;58:35–41.PubMedGoogle Scholar
  16. 16.
    Baquie P, Brukner P. Injuries presenting to an Australian sports medicine centre: a 12-month study. Clin J Sport Med. 1997;7:28–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Bertolotto M, Perrone R, Martinoli C, Rollandi GA, Patetta R, Derchi LE. High resolution ultrasound anatomy of normal Achilles tendon. Br J Radiol. 1995;68:986–991.PubMedGoogle Scholar
  18. 18.
    Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF. Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med. 2007;13:1219–1227.PubMedCrossRefGoogle Scholar
  19. 19.
    Birch HL. Tendon matrix composition and turnover in relation to functional requirements. Int J Exp Pathol. 2007;88:241–248.PubMedCrossRefGoogle Scholar
  20. 20.
    Birch HL, Bailey AJ, Goodship AE. Macroscopic ‘degeneration’ of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition. Equine Vet J. 1998;30:534–539.PubMedCrossRefGoogle Scholar
  21. 21.
    Bosman FT, Stamenkovic I. Functional structure and composition of the extracellular matrix. J Pathol. 2003;200:423–428.PubMedCrossRefGoogle Scholar
  22. 22.
    Bramono DS, Richmond JC, Weitzel PP, Kaplan DL, Altman GH. Matrix metalloproteinases and their clinical applications in orthopaedics. Clin Orthop Relat Res. 2004;428:272–285.PubMedCrossRefGoogle Scholar
  23. 23.
    Burniston JG, Tan LB, Goldspink DF. Beta2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle. J Appl Physiol. 2005;98:1379–1386.PubMedCrossRefGoogle Scholar
  24. 24.
    Chakravarti S. Functions of lumican and fibromodulin: lessons from knockout mice. Glycoconj J. 2002;19:287–293.PubMedCrossRefGoogle Scholar
  25. 25.
    Chuen FS, Chuk CY, Ping WY, Nar WW, Kim HL, Ming CK. Immunohistochemical characterization of cells in adult human patellar tendons. J Histochem Cytochem. 2004;52:1151–1157.PubMedCrossRefGoogle Scholar
  26. 26.
    Clegg PD, Strassburg S, Smith RK. Cell phenotypic variation in normal and damaged tendons. Int J Exp Pathol. 2007;88:227–235.PubMedCrossRefGoogle Scholar
  27. 27.
    Colige A, Vandenberghe I, Thiry M, Lambert CA, Van Beeumen J, Li SW, Prockop DJ, Lapiere CM, Nusgens BV. Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3. J Biol Chem. 2002;277:5756–5766.PubMedCrossRefGoogle Scholar
  28. 28.
    Cook JL, Feller JA, Bonar SF, Khan KM. Abnormal tenocyte morphology is more prevalent than collagen disruption in asymptomatic athletes’ patellar tendons. J Orthop Res. 2004;22:334–338.PubMedCrossRefGoogle Scholar
  29. 29.
    Corps AN, Robinson AH, Movin T, Costa ML, Hazleman BL, Riley GP. Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy. Rheumatology (Oxford). 2006;45:291–294.CrossRefGoogle Scholar
  30. 30.
    Corps AN, Robinson AH, Movin T, Costa ML, Ireland DC, Hazleman BL, Riley GP. Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies. Rheumatology (Oxford). 2004;43:969–972.CrossRefGoogle Scholar
  31. 31.
    Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol. 1997;136:729–743.PubMedCrossRefGoogle Scholar
  32. 32.
    Danielson P, Alfredson H, Forsgren S. In situ hybridization studies confirming recent findings of the existence of a local nonneuronal catecholamine production in human patellar tendinosis. Microsc Res Tech. 2007;70:908–911.PubMedCrossRefGoogle Scholar
  33. 33.
    Danielson P, Alfredson H, Forsgren S. Studies on the importance of sympathetic innervation, adrenergic receptors, and a possible local catecholamine production in the development of patellar tendinopathy (tendinosis) in man. Microsc Res Tech. 2007;70:310–324.PubMedCrossRefGoogle Scholar
  34. 34.
    de Mos M, van El B, DeGroot J, Jahr H, van Schie HT, van Arkel ER, Tol H, Heijboer R, van Osch GJ, Verhaar JA. Achilles tendinosis: changes in biochemical composition and collagen turnover rate. Am J Sports Med. 2007;35:1549–1556.PubMedCrossRefGoogle Scholar
  35. 35.
    Eriksen HA, Pajala A, Leppilahti J, Risteli J. Increased content of type III collagen at the rupture site of human Achilles tendon. J Orthop Res. 2002;20:1352–1357.PubMedCrossRefGoogle Scholar
  36. 36.
    Frey C, Zamora J. The effects of obesity on orthopaedic foot and ankle pathology. Foot Ankle Int. 2007;28:996–999.PubMedCrossRefGoogle Scholar
  37. 37.
    Frost P, Bonde JPE, Mikkelsen S, Andersen JH, Fallentin N, Kaergaard A, Thomsen JF. Risk of shoulder tendinitis in relation to shoulder loads in monotonous repetitive work. Am J Indust Med. 2002;41:11–18.CrossRefGoogle Scholar
  38. 38.
    Fu SC, Chan BP, Wang W, Pau HM, Chan KM, Rolf CG. Increased expression of matrix metalloproteinase 1 (MMP1) in 11 patients with patellar tendinosis. Acta Orthop Scand. 2002;73:658–662.PubMedCrossRefGoogle Scholar
  39. 39.
    Fu SC, Chan KM, Rolf CG. Increased deposition of sulfated glycosaminoglycans in human patellar tendinopathy. Clin J Sport Med. 2007;17:129–134.PubMedCrossRefGoogle Scholar
  40. 40.
    Fu SC, Wong YP, Chan BP, Pau HM, Cheuk YC, Lee KM, Chan KM. The roles of bone morphogenetic protein (BMP) 12 in stimulating the proliferation and matrix production of human patellar tendon fibroblasts. Life Sci. 2003;72:2965–2974.PubMedCrossRefGoogle Scholar
  41. 41.
    Gelberman RH, Steinberg D, Amiel D, Akeson W. Fibroblast chemotaxis after tendon repair. J Hand Surg (Am). 1991;16:686–693.CrossRefGoogle Scholar
  42. 42.
    Goncalves-Neto J, Witzel SS, Teodoro WR, Carvalho-Junior AE, Fernandes TD, Yoshinari HH. Changes in collagen matrix composition in human posterior tibial tendon dysfunction. Joint Bone Spine. 2002;69:189–194.PubMedCrossRefGoogle Scholar
  43. 43.
    Hardingham TE, Fosang AJ. Proteoglycans: many forms and many functions. Faseb J. 1992;6:861–870.PubMedGoogle Scholar
  44. 44.
    Harvie P, Ostlere SJ, Teh J, McNally EG, Clipsham K, Burston BJ, Pollard TC, Carr AJ. Genetic influences in the aetiology of tears of the rotator cuff. Sibling risk of a full-thickness tear. J Bone Joint Surg Br. 2004;86:696–700.PubMedCrossRefGoogle Scholar
  45. 45.
    Hashimoto G, Aoki T, Nakamura H, Tanzawa K, Okada Y. Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4). FEBS Lett. 2001;494:192–195.PubMedCrossRefGoogle Scholar
  46. 46.
    Hashimoto T, Nobuhara K, Hamada T. Pathologic evidence of degeneration as a primary cause of rotator cuff tear. Clin Orthop Relat Res. 2003;415:111–120.PubMedCrossRefGoogle Scholar
  47. 47.
    Holmes GB, Lin J. Etiologic factors associated with symptomatic achilles tendinopathy. Foot Ankle Int. 2006;27:952–959.PubMedGoogle Scholar
  48. 48.
    Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G. Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol. 2001;20:159–169.PubMedCrossRefGoogle Scholar
  49. 49.
    Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum. 2006;54:832–842.PubMedCrossRefGoogle Scholar
  50. 50.
    Jones GC, Riley GP. ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis. Arthritis Res Ther. 2005;7:160–169.PubMedCrossRefGoogle Scholar
  51. 51.
    Jozsa L, Balint JB, Kannus P, Reffy A, Barzo M. Distribution of blood groups in patients with tendon rupture. An analysis of 832 cases. J Bone Joint Surg Br. 1989;71:272–274.PubMedGoogle Scholar
  52. 52.
    Jozsa L, Barzo M, Balint JB. Correlations between the ABO blood group system and tendon rupture. Magy Traumatol Orthop Helyreallito Seb. 1990;33:101–104.PubMedGoogle Scholar
  53. 53.
    Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports. 2000;10:312–320.PubMedCrossRefGoogle Scholar
  54. 54.
    Kannus P, Jozsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am. 1991;73:1507–1525.PubMedGoogle Scholar
  55. 55.
    Kashiwagi M, Enghild JJ, Gendron C, Hughes C, Caterson B, Itoh Y, Nagase H. Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing. J Biol Chem. 2004;279:10109–10119.PubMedCrossRefGoogle Scholar
  56. 56.
    Kashiwagi M, Tortorella M, Nagase H, Brew K. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J Biol Chem. 2001;276:12501–12504.PubMedCrossRefGoogle Scholar
  57. 57.
    Khan KM, Cook JL, Bonar F, Harcourt P, Astrom M. Histopathology of common tendinopathies. Update and implications for clinical management. Sports Med. 1999;27:393–408.PubMedCrossRefGoogle Scholar
  58. 58.
    Kjaer M. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev. 2004;84:649–698.PubMedCrossRefGoogle Scholar
  59. 59.
    Kujala UM, Jarvinen M, Natri A, Lehto M, Nelimarkka O, Hurme M, Virta L, Finne J. ABO blood groups and musculoskeletal injuries. Injury. 1992;23:131–133.PubMedCrossRefGoogle Scholar
  60. 60.
    Kujala UM, Sarna S, Kaprio J. Cumulative incidence of achilles tendon rupture and tendinopathy in male former elite athletes. Clin J Sport Med. 2005;15:133–135.PubMedCrossRefGoogle Scholar
  61. 61.
    Lechner BE, Lim JH, Mercado ML, Fallon JR. Developmental regulation of biglycan expression in muscle and tendon. Muscle Nerve. 2006;34:347–355.PubMedCrossRefGoogle Scholar
  62. 62.
    Lehto M, Jozsa L, Kvist M, Jarvinen M, Balint BJ, Reffy A. Fibronectin in the ruptured human Achilles tendon and its paratenon. An immunoperoxidase study. Ann Chir Gynaecol. 1990;79:72–77.PubMedGoogle Scholar
  63. 63.
    Lejard V, Brideau G, Blais F, Salingcarnboriboon R, Wagner G, Roehrl MH, Noda M, Duprez D, Houillier P, Rossert J. Scleraxis and NFATc regulate the expression of the pro-alpha1(I) collagen gene in tendon fibroblasts. J Biol Chem. 2007;282:17665–17675.PubMedCrossRefGoogle Scholar
  64. 64.
    Lian O, Dahl J, Ackermann PW, Frihagen F, Engebretsen L, Bahr R. Pronociceptive and antinociceptive neuromediators in patellar tendinopathy. Am J Sports Med. 2006;34:1801–1808.PubMedCrossRefGoogle Scholar
  65. 65.
    Lian O, Scott A, Engebretsen L, Bahr R, Duronio V, Khan K. Excessive apoptosis in patellar tendinopathy in athletes. Am J Sports Med. 2007;35:605–611.PubMedCrossRefGoogle Scholar
  66. 66.
    Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB. Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med. 2004;32:1223–1229.PubMedCrossRefGoogle Scholar
  67. 67.
    Lou J, Tu Y, Burns M, Silva MJ, Manske P. BMP-12 gene transfer augmentation of lacerated tendon repair. J Orthop Res. 2001;19:1199–1202.PubMedCrossRefGoogle Scholar
  68. 68.
    Maffulli N, Barrass V, Ewen SW. Light microscopic histology of achilles tendon ruptures. A comparison with unruptured tendons. Am J Sports Med. 2000;28:857–863.PubMedGoogle Scholar
  69. 69.
    Maffulli N, Ewen SW, Waterston SW, Reaper J, Barrass V. Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing. Am J Sports Med. 2000;28:499–505.PubMedGoogle Scholar
  70. 70.
    Maffulli N, Sharma P, Luscombe KL. Achilles tendinopathy: aetiology and management. Journal of the Royal Society of Medicine. 2004;97(10):472–476.PubMedCrossRefGoogle Scholar
  71. 71.
    Magra M, Maffulli N. Matrix metalloproteases: a role in overuse tendinopathies. Br J Sports Med. 2005;39:789–791.PubMedCrossRefGoogle Scholar
  72. 72.
    Matheson S, Larjava H, Hakkinen L. Distinctive localization and function for lumican, fibromodulin and decorin to regulate collagen fibril organization in periodontal tissues. J Periodontal Res. 2005;40:312–324.PubMedCrossRefGoogle Scholar
  73. 73.
    Mokone GG, Gajjar M, September AV, Schwellnus MP, Greenberg J, Noakes TD, Collins M. The guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with achilles tendon injuries. Am J Sports Med. 2005;33:1016–1021.PubMedCrossRefGoogle Scholar
  74. 74.
    Mokone GG, Schwellnus MP, Noakes TD, Collins M. The COL5A1 gene and Achilles tendon pathology. Scand J Med Sci Sports. 2006;16:19–26.PubMedCrossRefGoogle Scholar
  75. 75.
    Molloy TJ, Kemp MW, Wang Y, Murrell GAC. Microarray analysis of the tendinopathic rat supraspinatus tendon: glutamate signaling and its potential role in tendon degeneration. J Appl Physiol. 2006;101:1702–1709.PubMedCrossRefGoogle Scholar
  76. 76.
    Molloy TJ, Wang Y, Horner A, Skerry TM, Murrell GAC. Microarray analysis of healing rat Achilles tendon: evidence for glutamate signalling mechanisms and embryonic gene expression in healing tendon tissue. J Orthop Res. 2006;24:842–855.PubMedCrossRefGoogle Scholar
  77. 77.
    Moreno M, Munoz R, Aroca F, Labarca M, Brandan E, Larrain J. Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway. Embo J. 2005;24:1397–1405.PubMedCrossRefGoogle Scholar
  78. 78.
    Murchison ND, Price BA, Conner DA, Keene DR, Olson EN, Tabin CJ, Schweitzer R. Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons. Development. 2007;134:2697–2708.PubMedCrossRefGoogle Scholar
  79. 79.
    Murray IR, Murray SA, MacKenzie K, Coleman S. How evidence based is the management of two common sports injuries in a sports injury clinic? Br J Sports Med. 2005;39:912–916; discussion 916.PubMedCrossRefGoogle Scholar
  80. 80.
    Nakama LH, King KB, Abrahamsson S, Rempel DM. VEGF, VEGFR-1, and CTGF cell densities in tendon are increased with cyclical loading: An in vivo tendinopathy model. J Orthop Res. 2006;24:393–400.PubMedCrossRefGoogle Scholar
  81. 81.
    Nakamura H, Fujii Y, Inoki I, Sugimoto K, Tanzawa K, Matsuki H, Miura R, Yamaguchi Y, Okada Y. Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites. J Biol Chem. 2000;275:38885–38890.PubMedCrossRefGoogle Scholar
  82. 82.
    Ohberg L, Alfredson H. Ultrasound guided sclerosis of neovessels in painful chronic Achilles tendinosis: pilot study of a new treatment. Br J Sports Med. 2002;36:173–175; discussion 176–177.PubMedCrossRefGoogle Scholar
  83. 83.
    Primakoff P, Myles DG. The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet. 2000;16:83–87.PubMedCrossRefGoogle Scholar
  84. 84.
    Pufe T, Petersen W, Tillmann B, Mentlein R. The angiogenic peptide vascular endothelial growth factor is expressed in foetal and ruptured tendons. Virchows Archiv. 2001;439:579–585.PubMedCrossRefGoogle Scholar
  85. 85.
    Richards PJ, Win T, Jones PW. The distribution of microvascular response in Achilles tendonopathy assessed by colour and power Doppler. Skeletal Radiol. 2005;34:336–342.PubMedCrossRefGoogle Scholar
  86. 86.
    Riley G. The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford). 2004;43:131–142.CrossRefGoogle Scholar
  87. 87.
    Riley GP. Gene expression and matrix turnover in overused and damaged tendons. Scand J Med Sci Sports. 2005;15:241–251.PubMedCrossRefGoogle Scholar
  88. 88.
    Riley GP, Curry V, DeGroot J, van El B, Verzijl N, Hazleman BL, Bank RA. Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol. 2002;21:185–195.PubMedCrossRefGoogle Scholar
  89. 89.
    Riley GP, Goddard MJ, Hazleman BL. Histopathological assessment and pathological significance of matrix degeneration in supraspinatus tendons. Rheumatology (Oxford). 2001;40:229–230.CrossRefGoogle Scholar
  90. 90.
    Riley GP, Harrall RL, Cawston TE, Hazleman BL, Mackie EJ. Tenascin-C and human tendon degeneration. Am J Pathol. 1996;149:933–943.PubMedGoogle Scholar
  91. 91.
    Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL. Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis. 1994;53:367–376.PubMedCrossRefGoogle Scholar
  92. 92.
    Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL. Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis. 1994;53:359–366.PubMedGoogle Scholar
  93. 93.
    Schubert TE, Weidler C, Lerch K, Hofstadter F, Straub RH. Achilles tendinosis is associated with sprouting of substance P positive nerve fibres. Ann Rheum Dis. 2005;64:1083–1086.PubMedCrossRefGoogle Scholar
  94. 94.
    Schweitzer R, Chyung JH, Murtaugh LC, Brent AE, Rosen V, Olson EN, Lassar A, Tabin CJ. Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments. Development. 2001;128:3855–3866.PubMedGoogle Scholar
  95. 95.
    Scott A, Ashe MC. Common tendinopathies in the upper and lower extremities. Curr Sports Med Rep. 2006;5:233–241.PubMedCrossRefGoogle Scholar
  96. 96.
    Scott A, Cook JL, Hart DA, Walker DC, Duronio V, Khan KM. Tenocyte responses to mechanical loading in vivo: a role for local insulin-like growth factor 1 signaling in early tendinosis in rats. Arthritis Rheum. 2007;56:871–881.PubMedCrossRefGoogle Scholar
  97. 97.
    Scott A, Khan KM, Heer J, Cook JL, Lian O, Duronio V. High strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat tibialis anterior model. Br J Sports Med. 2005;39:e25.PubMedCrossRefGoogle Scholar
  98. 98.
    Sein ML. Shoulder Pain in Elite Swimmers. Sydney, Australia: Medicine, University of New South Wales; 2006.Google Scholar
  99. 99.
    Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am. 2005;87:187–202.PubMedCrossRefGoogle Scholar
  100. 100.
    Skutek M, van Griensven M, Zeichen J, Brauer N, Bosch U. Cyclic mechanical stretching of human patellar tendon fibroblasts: activation of JNK and modulation of apoptosis. Knee Surg Sports Traumatol Arthrosc. 2003;11:122–129.PubMedGoogle Scholar
  101. 101.
    Soslowsky LJ, Thomopoulos S, Tun S, Flanagan CL, Keefer CC, Mastaw J, Carpenter JE. Neer Award 1999. Overuse activity injures the supraspinatus tendon in an animal model: a histologic and biomechanical study. J Shoulder Elbow Surg. 2000;9:79–84.PubMedCrossRefGoogle Scholar
  102. 102.
    Tanaka S, Petersen M, Cameron L. Prevalence and risk factors of tendinitis and related disorders of the distal upper extremity among U.S. workers: comparison to carpal tunnel syndrome. Am J Indust Med. 2001;39:328–335.CrossRefGoogle Scholar
  103. 103.
    Tang BL. ADAMTS: a novel family of extracellular matrix proteases. Int J Biochem Cell Biol. 2001;33:33–44.PubMedCrossRefGoogle Scholar
  104. 104.
    Thomopoulos S, Hattersley G, Rosen V, Mertens M, Galatz L, Williams GR, Soslowsky LJ. The localized expression of extracellular matrix components in healing tendon insertion sites: an in situ hybridization study. J Orthop Res. 2002;20:454–463.PubMedCrossRefGoogle Scholar
  105. 105.
    Tillander B, Franzen L, Norlin R. Fibronectin, MMP-1 and histologic changes in rotator cuff disease. J Orthop Res. 2002;20:1358–1364.PubMedCrossRefGoogle Scholar
  106. 106.
    Trebaul A, Chan EK, Midwood KS. Regulation of fibroblast migration by tenascin-C. Biochem Soc Trans. 2007;35(Pt 4):695–697.PubMedGoogle Scholar
  107. 107.
    Tsuzaki M, Yamauchi M, Banes AJ. Tendon collagens: extracellular matrix composition in shear stress and tensile components of flexor tendons. Connect Tissue Res. 1993;29:141–152.PubMedCrossRefGoogle Scholar
  108. 108.
    Vu TH, Werb Z. Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev. 2000;14:2123–2133.PubMedCrossRefGoogle Scholar
  109. 109.
    Wadhwa S, Embree MC, Bi Y, Young MF. Regulation, regulatory activities, and function of biglycan. Crit Rev Eukaryot Gene Expr. 2004;14:301–315.PubMedCrossRefGoogle Scholar
  110. 110.
    Waggett AD, Ralphs JR, Kwan AP, Woodnutt D, Benjamin M. Characterization of collagens and proteoglycans at the insertion of the human Achilles tendon. Matrix Biol. 1998;16:457–470.PubMedCrossRefGoogle Scholar
  111. 111.
    Wang F, Murrell GA, Wang MX. Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression. J Orthop Res. 2007;25:378–389.PubMedCrossRefGoogle Scholar
  112. 112.
    Wang QW, Chen ZL, Piao YJ. Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein (BMP) 12 gene transfer. J Biosci Bioeng. 2005;100:418–422.PubMedCrossRefGoogle Scholar
  113. 113.
    Westling J, Gottschall PE, Thompson VP, Cockburn A, Perides G, Zimmermann DR, Sandy JD. ADAMTS4 (aggrecanase-1) cleaves human brain versican V2 at Glu405-Gln406 to generate glial hyaluronate binding protein. Biochem J. 2004;377(Pt 3):787–795.PubMedGoogle Scholar
  114. 114.
    Wolfman NM, Hattersley G, Cox K, Celeste AJ, Nelson R, Yamaji N, Dube JL, DiBlasio-Smith E, Nove J, Song JJ, Wozney JM, Rosen V. Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J Clin Invest. 1997;100:321–330.PubMedCrossRefGoogle Scholar
  115. 115.
    Yanagishita M. Function of proteoglycans in the extracellular matrix. Acta Pathol Jpn. 1993;43:283–293.PubMedGoogle Scholar
  116. 116.
    Yoon JH, Halper J. Tendon proteoglycans: biochemistry and function. J Musculoskelet Neuronal Interact. 2005;5:22–34.PubMedGoogle Scholar
  117. 117.
    Yuan J, Murrell GA, Wei AQ, Wang MX. Apoptosis in rotator cuff tendonopathy. J Orthop Res. 2002;20:1372–1379.PubMedCrossRefGoogle Scholar
  118. 118.
    Yuan J, Murrell GAC, Trickett A, Wang MX. Involvement of cytochrome c release and caspase-3 activation in the oxidative stress-induced apoptosis in human tendon fibroblasts. Biochimica et Biophysica Acta. 2003;1641:35–41.PubMedGoogle Scholar

Copyright information

© The Association of Bone and Joint Surgeons 2008

Authors and Affiliations

  1. 1.Orthopaedic Research Institute, The St. George Hospital University of New South WalesSydneyAustralia

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