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Expression of matrix metalloproteinases 1, 3, and 9 in differing extents of tendon retraction in the torn rotator cuff

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Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

Differing extents of tendon retraction are found in full-thickness rotator cuff tears. The pathophysiologic context of tendon degeneration and the extent of tendon retraction are unclear. Tendon integrity depends on the extracellular matrix, which is regulated by matrix metalloproteinases (MMP). It is unknown which enzymes play a role in tendon degeneration. The hypotheses are that (1) the expression of MMPs 1, 3, and 9 is altered in the torn rotator cuff when compared with healthy tendon samples; and (2) that there is a relationship between MMP expression and the extent of tendon retraction in the torn cuff.

Methods

Rotator cuff tendon samples of 33 patients with full-thickness rotator cuff tears (Bateman grade III) were harvested during reconstructive surgery. Samples were dehydrated and paraffin-embedded. Immunohistologic determination of MMP 1, 3, and 9 expression was performed by staining sample slices with MMP antibody. The extent of tendon retraction was determined intraoperatively according to Patte’s classification and patients were assigned to 4 groups (control group, and by tendon retraction grade Patte I-III). The control group consisted of six healthy tendon samples.

Results

Expression of MMPs 1 and 9 was significantly higher in torn cuff samples than in healthy tendons whereas MMP 3 expression was significantly decreased (P < 0.05). MMP 9 expression significantly increased with rising extent of tendon retraction in the torn cuff (P < 0.05). No significant association was found between expression of MMPs 1 and 3 and the rising extent of tendon retraction by Patte’s classification.

Conclusion

Elevated expression of MMPs 1 and 9 as well as decreased MMP 3 expression can be detected in torn rotator cuff tendon tissue. There is a significant association between the extent of tendon retraction and MMP 9 expression. The results of this study give evidence that early surgical treatment of small and partial-thickness rotator cuff tears is required.

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References

  1. Alfredson H (2005) The chronic painful Achilles and patellar tendon: research on basic biology and treatment. Scand J Med Sci Sports 15:252–259

    Article  PubMed  Google Scholar 

  2. Andarawis-Puri N, Ricchetti ET, Soslowsky LJ (2009) Rotator cuff tendon strain correlates with tear propagation. J Biomech 42:158–163

    Article  PubMed  Google Scholar 

  3. Asundi KR, Rempel DM (2008) Cyclic loading inhibits expression of MMP-3 but not MMP-1 in an in vitro rabbit flexor tendon model. Clin Biomech (Bristol, Avon) 23:117–121

    Article  Google Scholar 

  4. Bateman JE (1963) The diagnosis and treatment of ruptures of the rotator cuff. Surg Clin North Am 43:1523–1530

    PubMed  CAS  Google Scholar 

  5. Bedi A, Fox AJ, Kovacevic D, Deng XH, Warren RF, Rodeo SA (2010) Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair. Am J Sports Med 38:308–317

    Article  PubMed  Google Scholar 

  6. Budoff JE, Rodin D, Ochiai D, Nirschl RP (2005) Arthroscopic rotator cuff debridement without decompression for the treatment of tendinosis. Arthroscopy 21:1081–1089

    Article  PubMed  Google Scholar 

  7. Chong AK, Ang AD, Goh JC, Hui JH, Lim AY, Lee EH, Lim BH (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

    Article  PubMed  Google Scholar 

  8. Dudhia J, Scott CM, Draper ER, Heinegard D, Pitsillides AA, Smith RK (2007) Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell 6:547–556

    Article  PubMed  CAS  Google Scholar 

  9. Fu SC, Chan BP, Wang W, Pau HM, Chan KM, Rolf CG (2002) Increased expression of matrix metalloproteinase 1 (MMP1) in 11 patients with patellar tendinosis. Acta Orthop Scand 73:658–662

    Article  PubMed  Google Scholar 

  10. Fuchs S, Skwara A, Bloch M, Dankbar B (2004) Differential induction and regulation of matrix metalloproteinases in osteoarthritic tissue and fluid synovial fibroblasts. Osteoarthr Cartil 12:409–418

    Article  PubMed  CAS  Google Scholar 

  11. Gohlke F (1993) Ultrasonographic appearance of the rotator cuff in elderly subjects. Orthopade 22:288–293

    PubMed  CAS  Google Scholar 

  12. Gulotta LV, Kovacevic D, Montgomery S, Ehteshami JR, Packer JD, Rodeo SA (2010) Stem cells genetically modified with the developmental gene MT1-MMP improve regeneration of the supraspinatus tendon-to-bone insertion site. Am J Sports Med 38:1429–1437

    Article  PubMed  Google Scholar 

  13. Gwilym SE, Watkins B, Cooper CD, Harvie P, Auplish S, Pollard TC, Rees JL, Carr AJ (2009) Genetic influences in the progression of tears of the rotator cuff. J Bone Joint Surg Br 91:915–917

    Article  PubMed  CAS  Google Scholar 

  14. Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G (2001) Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol 20:159–169

    Article  PubMed  CAS  Google Scholar 

  15. Irie T, Takahata M, Majima T, Abe Y, Komatsu M, Iwasaki N, Minami A (2010) Effect of selective estrogen receptor modulator/raloxifene analogue on proliferation and collagen metabolism of tendon fibroblast. Connect Tissue Res 51:179–187

    Article  PubMed  CAS  Google Scholar 

  16. Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP (2006) Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum 54:832–842

    Article  PubMed  CAS  Google Scholar 

  17. Karaoglu S, Celik C, Korkusuz P (2009) The effects of bone marrow or periosteum on tendon-to-bone tunnel healing in a rabbit model. Knee Surg Sports Traumatol Arthrosc 17:170–178

    Article  PubMed  Google Scholar 

  18. Kjaer M (2004) Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 84:649–698

    Article  PubMed  CAS  Google Scholar 

  19. Lehmann LJ, Schollmeyer A, Stoeve J, Scharf HP (2009) Biochemical analysis of the synovial fluid of the shoulder joint in patients with and without rotator cuff tears. Z Orthop Unfall 148:90–94

    Article  PubMed  Google Scholar 

  20. Lewis JS (2009) Rotator cuff tendinopathy. Br J Sports Med 43:236–241

    Article  PubMed  CAS  Google Scholar 

  21. Lewis JS (2009) Rotator cuff tendinopathy/subacromial impingement syndrome: is it time for a new method of assessment? Br J Sports Med 43:259–264

    Article  PubMed  CAS  Google Scholar 

  22. Lewis JS, Sandford FM (2009) Rotator cuff tendinopathy: is there a role for polyunsaturated fatty acids and antioxidants? J Hand Ther 22:49–55 quiz 56

    Article  PubMed  Google Scholar 

  23. Liu X, Han Q, Sun R, Li Z (2008) Dexamethasone regulation of matrix metalloproteinase expression in experimental pneumococcal meningitis. Brain Res 1207:237–243

    Article  PubMed  CAS  Google Scholar 

  24. Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB (2004) Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 32:1223–1229

    Article  PubMed  Google Scholar 

  25. Lohr JF, Uhthoff HK (1990) The microvascular pattern of the supraspinatus tendon. Clin Orthop Relat Res 254:35–38

    PubMed  Google Scholar 

  26. Matsui Y, Maeda M, Nakagami W, Iwata H (1998) The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation. Spine (Phila Pa 1976) 23:863–868 discussion 868-869

    Article  CAS  Google Scholar 

  27. Neer CS II (1972) Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report. J Bone Joint Surg Am 54:41–50

    PubMed  Google Scholar 

  28. Nho SJ, Yadav H, Shindle MK, Macgillivray JD (2008) Rotator cuff degeneration: etiology and pathogenesis. Am J Sports Med 36:987–993

    Article  PubMed  Google Scholar 

  29. Pasternak B, Aspenberg P (2009) Metalloproteinases and their inhibitors-diagnostic and therapeutic opportunities in orthopedics. Acta Orthop 80:693–703

    Article  PubMed  Google Scholar 

  30. Patte D (1990) Classification of rotator cuff lesions. Clin Orthop Relat Res 254:81–86

    PubMed  Google Scholar 

  31. Pauly S, Klatte F, Strobel C, Schmidmaier G, Greiner S, Scheibel M, Wildemann B (2010) Characterization of tendon cell cultures of the human rotator cuff. Eur Cell Mater 20:84–97

    PubMed  CAS  Google Scholar 

  32. Perry SM, Getz CL, Soslowsky LJ (2009) After rotator cuff tears, the remaining (intact) tendons are mechanically altered. J Shoulder Elbow Surg 18:52–57

    Article  PubMed  Google Scholar 

  33. Raleigh SM, van der Merwe L, Ribbans WJ, Smith RK, Schwellnus MP, Collins M (2009) Variants within the MMP3 gene are associated with Achilles tendinopathy: possible interaction with the COL5A1 gene. Br J Sports Med 43:514–520

    Article  PubMed  CAS  Google Scholar 

  34. Riley G (2004) The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford) 43:131–142

    Article  CAS  Google Scholar 

  35. Riley G (2008) Tendinopathy–from basic science to treatment. Nat Clin Pract Rheumatol 4:82–89

    Article  PubMed  Google Scholar 

  36. Riley GP (2005) Gene expression and matrix turnover in overused and damaged tendons. Scand J Med Sci Sports 15:241–251

    Article  PubMed  CAS  Google Scholar 

  37. Schofer MD, Quante M, Peterlein CD, Timmesfeld N, Phan K, Fuchs-Winkelmann S (2009) Operative and follow-up treatment of rotator cuff tears–the current situation. Z Orthop Unfall 147:321–326

    Article  PubMed  CAS  Google Scholar 

  38. Tajana MS, Murena L, Valli F, Passi A, Grassi FA (2009) Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease. Chir Organi Mov 93(Suppl 1):S41–S48

    PubMed  Google Scholar 

  39. Tondreau T, Meuleman N, Stamatopoulos B, De Bruyn C, Delforge A, Dejeneffe M, Martiat P, Bron D, Lagneaux L (2009) In vitro study of matrix metalloproteinase/tissue inhibitor of metalloproteinase production by mesenchymal stromal cells in response to inflammatory cytokines: the role of their migration in injured tissues. Cytotherapy 11:559–569

    Article  PubMed  CAS  Google Scholar 

  40. Tsai WC, Hsu CC, Chang HN, Lin YC, Lin MS, Pang JH (2010) Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13 without affecting expressions of types I and III collagen in tendon cells. J Orthop Res 28:487–491

    PubMed  CAS  Google Scholar 

  41. Voloshin I, Gelinas J, Maloney MD, O’Keefe RJ, Bigliani LU, Blaine TA (2005) Proinflammatory cytokines and metalloproteases are expressed in the subacromial bursa in patients with rotator cuff disease. Arthroscopy 21:1076

    PubMed  Google Scholar 

  42. Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA (2006) The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am 88:1699–1704

    Article  PubMed  Google Scholar 

  43. Yoshihara Y, Hamada K, Nakajima T, Fujikawa K, Fukuda H (2001) Biochemical markers in the synovial fluid of glenohumeral joints from patients with rotator cuff tear. J Orthop Res 19:573–579

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank the Kempkes-Foundation (Marburg, Germany) for being the sole financial supporters of this study. We also thank Soeren Schwuchow for his support in performing the histologic analyses.

Conflict of interest

The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Orthopedics and Rheumatology, University Hospital Marburg, Baldingerstrasse, 35043, Marburg, Germany

    Stefan Lakemeier, Juliane Braun, Turgay Efe, Christian Foelsch, Eleni Archontidou-Aprin, Susanne Fuchs-Winkelmann, Juergen R. J. Paletta & Markus D. Schofer

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  1. Stefan Lakemeier
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  2. Juliane Braun
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  3. Turgay Efe
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Correspondence to Stefan Lakemeier.

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Lakemeier, S., Braun, J., Efe, T. et al. Expression of matrix metalloproteinases 1, 3, and 9 in differing extents of tendon retraction in the torn rotator cuff. Knee Surg Sports Traumatol Arthrosc 19, 1760–1765 (2011). https://doi.org/10.1007/s00167-010-1367-y

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