Skip to main content

Advertisement

SpringerLink
Log in

Cellular response and extracellular matrix breakdown in rotator cuff tendon rupture

  • Basic Science
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to investigate the relationship between the disruption of ECM and cellular events including autophagic cell death, apoptosis and cell differentiation into myofibroblasts in the degenerative rotator cuff tendon.

Methods

Tendon samples were collected from 30 patients undergoing surgery for rotator cuff tears. Apoptosis, autophagic cell death and myofibroblasts of the tendon cells in the ruptured rotator cuff tendon were detected by immunohistochemical staining. The distribution of autophagic cell death, apoptosis, myofibroblasts and cell density were assessed and correlated with the disruption of ECM which was graded 0–3 points using a customized scoring system.

Results

The highest percentage of autophagic cell death (51.9 ± 1.5%) was observed in grade 2 matrix, significantly different from that in matrix graded 0, 1 and 3 (P2Vs0 < 0.001; P2Vs1 < 0.001; P2Vs3 = 0.008, respectively). The highest apoptosis (34.8 ± 1.6%) was found in grade 3 matrix (P3Vs0 < 0.001; P3Vs1 < 0.001; P3Vs2 = 0.044, respectively). The percentage of myofibroblasts significantly increased as the ECM degenerated, with the highest percentage in grade 3 matrix (19.8 ± 1.3%) (P3Vs0 < 0.001; P3Vs11 < 0.001; P3Vs2 = 0.044, respectively). The total cell density varied with the grade of ECM, with maximum cell density in the matrix that was graded 1 (674 ± 27) and minimum cell density in matrix 3 area (395 ± 17) (P1Vs3 < 0.001).

Conclusion

This study indicates that autophagic cell death, apoptosis and myofibroblast cell differentiation occur in ruptured rotator cuff tissue. These cellular events are closely related to the extent of damage to the ECM structure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Yuan J, Murrell GA, Wei AQ, Wang MX (2002) Apoptosis in rotator cuff tendonopathy. J Orthop Res 20(6):1372–1379

    Article  PubMed  Google Scholar 

  2. Tuoheti Y, Itoi E, Pradhan RL, Wakabayashi I, Takahashi S, Minagawa H et al (2005) Apoptosis in the supraspinatus tendon with stage II subacromial impingement. J Shoulder Elbow Surg 14(5):535–541

    Article  PubMed  Google Scholar 

  3. Lian O, Scott A, Engebretsen L, Bahr R, Duronio V, Khan K (2007) Excessive apoptosis in patellar tendinopathy in athletes. Am J Sports Med 35(4):605–611

    Article  PubMed  Google Scholar 

  4. Yuan J, Wang MX, Murrell GA (2003) Cell death and tendinopathy. Clin Sports Med 22(4):693–701

    Article  PubMed  Google Scholar 

  5. Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306(5698):990–995

    Article  CAS  PubMed  Google Scholar 

  6. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441(7095):880–884

    Article  CAS  PubMed  Google Scholar 

  7. Komatsu M, Wang QJ, Holstein GR, Friedrich VL Jr, Iwata J, Kominami E et al (2007) Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration. Proc Natl Acad Sci USA 104(36):14489–14494

    Article  CAS  PubMed  Google Scholar 

  8. Yang Y, Fukui K, Koike T, Zheng X (2007) Induction of autophagy in neurite degeneration of mouse superior cervical ganglion neurons. Eur J Neurosci 26(10):2979–2988

    Article  PubMed  Google Scholar 

  9. Jester JV, Petroll WM, Barry PA, Cavanagh HD (1995) Expression of alpha-smooth muscle (alpha-SM) actin during corneal stromal wound healing. Invest Ophthalmol Vis Sci 36(5):809–819

    CAS  PubMed  Google Scholar 

  10. Thampatty BP, Wang JH (2007) A new approach to study fibroblast migration. Cell Motil Cytoskeleton 64(1):1–5

    Article  CAS  PubMed  Google Scholar 

  11. Knaapen MW, Davies MJ, De Bie M, Haven AJ, Martinet W, Kockx MM (2001) Apoptotic versus autophagic cell death in heart failure. Cardiovasc Res 51(2):304–312

    Article  CAS  PubMed  Google Scholar 

  12. Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM (2006) Detection of autophagy in tissue by standard immunohistochemistry: possibilities and limitations. Autophagy 2(1):55–57

    PubMed  Google Scholar 

  13. Mistiaen WP, Somers P, Knaapen MW, Kockx MM (2006) Autophagy as mechanism for cell death in degenerative aortic valve disease. Autophagy 2(3):221–223

    CAS  PubMed  Google Scholar 

  14. Somers P, Knaapen M, Kockx M, van Cauwelaert P, Bortier H, Mistiaen W (2006) Histological evaluation of autophagic cell death in calcified aortic valve stenosis. J Heart Valve Dis 15(1):43–47 discussion 8

    PubMed  Google Scholar 

  15. Ferraro E, Cecconi F (2007) Autophagic and apoptotic response to stress signals in mammalian cells. Arch Biochem Biophys 462(2):210–219

    Article  CAS  PubMed  Google Scholar 

  16. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8(9):741–752

    Article  CAS  PubMed  Google Scholar 

  17. Bursch W (2001) The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ 8(6):569–581

    Article  CAS  PubMed  Google Scholar 

  18. Anglade P, Vyas S, Javoy-Agid F, Herrero MT, Michel PP, Marquez J et al (1997) Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol Histopathol 12(1):25–31

    CAS  PubMed  Google Scholar 

  19. Bahr BA, Bendiske J (2002) The neuropathogenic contributions of lysosomal dysfunction. J Neurochem 83(3):481–489

    Article  CAS  PubMed  Google Scholar 

  20. Martinet W, Knaapen MW, Kockx MM, De Meyer GR (2010) Autophagy in cardiovascular disease. Trends Mol Med 7(1):40–47

    Google Scholar 

  21. Kaneda D, Sugie K, Yamamoto A, Matsumoto H, Kato T, Nonaka I et al (2003) A novel form of autophagic vacuolar myopathy with late-onset and multiorgan involvement. Neurology 61(1):128–131

    CAS  PubMed  Google Scholar 

  22. Kalimo H, Savontaus ML, Lang H, Paljarvi L, Sonninen V, Dean PB et al (1988) X-linked myopathy with excessive autophagy: a new hereditary muscle disease. Ann Neurol 23(3):258–265

    Article  CAS  PubMed  Google Scholar 

  23. Adams CS, Horton WE Jr (1998) Chondrocyte apoptosis increases with age in the articular cartilage of adult animals. Anat Rec 250(4):418–425

    Article  CAS  PubMed  Google Scholar 

  24. Lui PP, Cheuk YC, Hung LK, Fu SC, Chan KM (2007) Increased apoptosis at the late stage of tendon healing. Wound Repair Regen 15(5):702–707

    Article  PubMed  Google Scholar 

  25. Premdas J, Tang JB, Warner JP, Murray MM, Spector M (2001) The presence of smooth muscle actin in fibroblasts in the torn human rotator cuff. J Orthop Res 19(2):221–228

    Article  CAS  PubMed  Google Scholar 

  26. Murray MM, Spector M (1999) Fibroblast distribution in the anteromedial bundle of the human anterior cruciate ligament: the presence of alpha-smooth muscle actin-positive cells. J Orthop Res 17(1):18–27

    Article  CAS  PubMed  Google Scholar 

  27. Russell JE, Manske PR (1990) Collagen synthesis during primate flexor tendon repair in vitro. J Orthop Res 8(1):13–20

    Article  CAS  PubMed  Google Scholar 

  28. Lindsay WK, Thomson HG (1960) Digital flexor tendons: an experimental study. Part I. The significance of each component of the flexor mechanismhin tendon healing. Br J Plast Surg 12:289–316

    Article  CAS  PubMed  Google Scholar 

  29. Kajikawa Y, Morihara T, Watanabe N, Sakamoto H, Matsuda K, Kobayashi M et al (2007) GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing. J Cell Physiol 210(3):684–691

    Article  CAS  PubMed  Google Scholar 

  30. Gelberman RH, Amiel D, Harwood F (1992) Genetic expression for type I procollagen in the early stages of flexor tendon healing. J Hand Surg [Am] 17(3):551–558

    Article  CAS  Google Scholar 

  31. Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R (1995) In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology 21(5):1465–1468

    CAS  PubMed  Google Scholar 

  32. Chen YJ, Wang CJ, Yang KD, Kuo YR, Huang HC, Huang YT et al (2004) Extracorporeal shock waves promote healing of collagenase-induced Achilles tendinitis and increase TGF-beta1 and IGF-I expression. J Orthop Res 22(4):854–861

    Article  CAS  PubMed  Google Scholar 

  33. Chen J, Wang A, Xu J, Zheng M (2010) In chronic lateral epicondylitis, apoptosis and autophagic cell death occur in the extensor carpi radialis brevis tendon. J Shoulder Elbow Surg 19(3):355–362

    Article  PubMed  Google Scholar 

  34. Chen JM, Willers C, Xu J, Wang A, Zheng MH (2007) Autologous tenocyte therapy using porcine-derived bioscaffolds for massive rotator cuff defect in rabbits. Tissue Eng 13(7):1479–1491

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the internal funding from Centre for Orthopaedic Research.

Author information

Authors and Affiliations

  1. Centre for Orthopaedic Research, School of Surgery, University of Western Australia, M Block, QE2 Medical Centre, Nedlands, Perth, WA, 6009, Australia

    Bing Wu, Jimin Chen, Tammyl Dela Rosa, Qian Yu, Allan Wang, Jiake Xu & Ming-Hao Zheng

  2. Department of Orthopaedics, Shaoxing People’s Hospital, 312000, Shaoxing, China

    Qian Yu

Authors
  1. Bing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jimin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tammyl Dela Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Allan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiake Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ming-Hao Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ming-Hao Zheng.

Additional information

B. Wu and J. Chen contributed equally to this project.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, B., Chen, J., Rosa, T.D. et al. Cellular response and extracellular matrix breakdown in rotator cuff tendon rupture. Arch Orthop Trauma Surg 131, 405–411 (2011). https://doi.org/10.1007/s00402-010-1157-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00402-010-1157-5

Keywords

Search

Navigation