Skip to main content
SpringerLink
Log in

Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions

  • EXPERIMENTAL STUDY
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

To examine healing adaptations over 17 weeks post Achilles tendon (AT) rupture in the injured region (IR) compared to an uninjured region (UIR) of the AT.

Methods

Twenty-four rats were subjected to a complete right-sided AT rupture, while the left side served as a control. ATs were harvested at 1, 2, 8 and 17 weeks post-rupture and stained with antibodies specific to Collagen type I (Col I) and II (Col II) as well as Alcian Blue and Picrosirius Red staining techniques. Histopathological changes, proteoglycan content, collagen alignment and immunoexpression were assessed.

Results

Both regions examined, IR and UIR, exhibited over weeks 1–17 similar healing adaptations of increasing collagen alignment, decreasing Col I immunoexpression, as well as increasing proteoglycan content and Col II occurrence. Increased proteoglycan content was found already at week 2 in the UIR, while it first increased at week 8 in the IR. The area positive to Col II was increased compared to controls at week 8 in the UIR, whereas it first raised at week 17 in the IR. Collagen disorganization successively declined to reach control levels at week 17 in the UIR, but was still higher in the IR.

Conclusion

This study demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions. These changes including the pathologic heterotopic mineralization and chondrogenic differentiation observed in both regions may have implications in the choice of rehabilitation regimes in order to prevent secondary rupture.

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
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Abraham T, Fong G, Scott A (2011) Second harmonic generation analysis of early Achilles tendinosis in response to in vivo mechanical loading. BMC Musculoskelet Disord 12:26

    Article  Google Scholar 

  2. Aikawa E, Whittaker P, Farber M et al (2006) Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering. Circulation 113:1344–1352

    Article  Google Scholar 

  3. Asai S, Otsuru S, Candela ME, Enomoto-Iwamoto M et al (2014) Tendon progenitor cells in injured tendons have strong chondrogenic potential: the CD105-negative subpopulation induces chondrogenic degeneration. Stem Cells 32:3266–3277

    Article  CAS  Google Scholar 

  4. Ateschrang A, Gratzer C, Weise K (2008) Incidence and effect of calcifications after open-augmented Achilles tendon repair. Arch Orthop Trauma Surg 128:1087–1092

    Article  Google Scholar 

  5. Bring DK, Paulson K, Renstrom P et al (2012) Residual substance P levels after capsaicin treatment correlate with tendon repair. Wound Repair Regen 20:50–60

    Article  Google Scholar 

  6. Burssens A, Forsyth R, Bongaerts W et al (2013) Arguments for an increasing differentiation towards fibrocartilaginous components in midportion Achilles tendinopathy. Knee Surg Sports Traumatol Arthrosc 21:1459–1467

    Article  CAS  Google Scholar 

  7. Checa S, Rausch MK, Petersen A et al (2015) The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization. Biomech Model Mechanobiol 14:1–13

    Article  Google Scholar 

  8. Corradino B, Di Lorenzo S, Calamia C et al (2015) Surgical Repair Of Acute Achilles tendon rupture with an end-to-end tendon suture and tendon flap. Injury 46:1637–1640

    Article  CAS  Google Scholar 

  9. de Mos M, Koevoet W, van Schie HT et al (2009) In vitro model to study chondrogenic differentiation in tendinopathy. Am J Sports Med 37:1214–1222

    Article  Google Scholar 

  10. Dyment NA, Kazemi N, Aschbacher-Smith LE et al (2012) The relationships among spatiotemporal collagen gene expression, histology, and biomechanics following full-length injury in the murine patellar tendon. J Orthop Res 30:28–36

    Article  CAS  Google Scholar 

  11. Erdogan F, Aydingoz O, Kesmezacar H et al (2004) Calcification of the patellar tendon after ACL reconstruction. A case report with long-term follow-up. Knee Surg Sports Traumatol Arthrosc 12:277–279

    Article  Google Scholar 

  12. Finlay S, Seedhom BB, Carey DO et al (2016) In vitro engineering of high modulus cartilage-like constructs. Tissue Eng Part C Methods 22:382–397

    Article  CAS  Google Scholar 

  13. Hast MW, Zuskov A, Soslowsky LJ (2014) The role of animal models in tendon research. Bone Jt Res 3:193–202

    Article  CAS  Google Scholar 

  14. Khayyeri H, Blomgran P, Hammerman M et al (2017) Achilles tendon compositional and structural properties are altered after unloading by botox. Sci Rep 7:13067

    Article  Google Scholar 

  15. Lattouf R, Younes R, Lutomski D et al (2014) Picrosirius red staining: a useful tool to appraise collagen networks in normal and pathological tissues. J Histochem Cytochem 62:751–758

    Article  Google Scholar 

  16. Lemme NJ, Li NY, DeFroda SF et al (2018) Epidemiology of Achilles tendon ruptures in the United States: athletic and nonathletic injuries from 2012 to 2016. Orthop J Sports Med 6:2325967118808238

    Article  Google Scholar 

  17. Li HY, Hua YH (2016) Achilles tendinopathy: current concepts about the basic science and clinical treatments. Biomed Res Int 2016:6492597

    PubMed  PubMed Central  Google Scholar 

  18. Lin TW, Cardenas L, Soslowsky LJ (2004) Biomechanics of tendon injury and repair. J Biomech 37(6):865–877

    Article  Google Scholar 

  19. Longo UG, Ronga M, Maffulli N (2009) Achilles tendinopathy. Sports Med Arthrosc Rev 17:112–126

    Article  Google Scholar 

  20. Lui PP, Chan LS, Lee YW et al (2010) Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model. Rheumatology (Oxford) 49:231–239

    Article  CAS  Google Scholar 

  21. Lui PP, Fu SC, Chan LS et al (2009) Chondrocyte phenotype and ectopic ossification in collagenase-induced tendon degeneration. J Histochem Cytochem 57:91–100

    Article  CAS  Google Scholar 

  22. Maffulli N (1999) Rupture of the Achilles tendon. J Bone Jt Surg Am 81:1019–1036

    Article  CAS  Google Scholar 

  23. Magnusson SP, Langberg H, Kjaer M (2010) The pathogenesis of tendinopathy: balancing the response to loading. Nat Rev Rheumatol 6:262–268

    Article  Google Scholar 

  24. Milz S, Benjamin M, Putz R (2005) Molecular parameters indicating adaptation to mechanical stress in fibrous connective tissue. Adv Anat Embryol Cell Biol 178:1–71

    Article  CAS  Google Scholar 

  25. Müller SA, Todorov A, Heisterbach PE et al (2015) Tendon healing: an overview of physiology, biology, and pathology of tendon healing and systematic review of state of the art in tendon bioengineering. Knee Surg Sports Traumatol Arthrosc 23:2097–2105

    Article  Google Scholar 

  26. Olaleye OA, Zahn H (2008) An unusual second rupture of the Achilles tendon: a case report. Foot Ankle J 1:3

    Google Scholar 

  27. Runesson E, Ackermann P, Karlsson J et al (2015) Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing. BMC Musculoskelet Disord 16:212

    Article  Google Scholar 

  28. Sagarriga Visconti C, Kavalkovich K, Wu J et al (1996) Biochemical analysis of collagens at the ligament-bone interface reveals presence of cartilage-specific collagens. Arch Biochem Biophys 328:135–142

    Article  CAS  Google Scholar 

  29. Schriefl AJ, Reinisch AJ, Sankaran S et al (2012) Quantitative assessment of collagen fibre orientations from two-dimensional images of soft biological tissues. J R Soc Interface 9:3081–3093

    Article  CAS  Google Scholar 

  30. Sharma P, Maffulli N (2006) Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact 6:181–190

    CAS  PubMed  Google Scholar 

  31. Silva FS, Bortolin RH, Araújo DN et al (2017) Exercise training ameliorates matrix metalloproteinases 2 and 9 messenger RNA expression and mitigates adverse left ventricular remodeling in streptozotocin-induced diabetic rats. Cardiovasc Pathol 29:37–44

    Article  CAS  Google Scholar 

  32. Tekari A, Luginbuehl R, Hofstetter W et al (2014) Chondrocytes expressing intracellular collagen type II enter the cell cycle and co-express collagen type I in monolayer culture. J Orthop Res 32:1503–1511

    Article  CAS  Google Scholar 

  33. Voleti PB, Buckley MR, Soslowsky LJ (2012) Tendon healing: repair and regeneration. Annu Rev Biomed Eng 14:47–71

    Article  CAS  Google Scholar 

  34. Yang G, Rothrauff BB, Tuan RS (2013) Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today 99:203–222

    Article  CAS  Google Scholar 

  35. Zhang C, Zhang Y, Zhong B et al (2016) SMAD7 prevents heterotopic ossification in a rat Achilles tendon injury model via regulation of endothelial-mesenchymal transition. FEBS J 283:1275–1285

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Eva Runesson for her assistance in preparing this manuscript.

Funding

This Research had support of the Sahlgrenska University Hospital, Gothenburg, Sweden (ALF project 164031, ALFGBG-442011).

Author information

Authors and Affiliations

  1. Department of Health Sciences, Federal University of the Semiarid Region, Mossoró, Brazil

    Flávio Santos da Silva

  2. Department of Morphology, Federal University of Rio Grande do Norte, Natal, Brazil

    Bento João Abreu

  3. Gothenburg University, Gothenburg, Sweden

    Bengt I. Eriksson

  4. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Paul W. Ackermann

  5. Department of Orthopedic Surgery, Karolinska University Hospital, 17176, Stockholm, Sweden

    Paul W. Ackermann

Authors
  1. Flávio Santos da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bento João Abreu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bengt I. Eriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul W. Ackermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BIE and PWA conceived and designed the study. FSS performed the data collection. FSS and BJA performed the data analysis and statistics, prepared figures, and wrote the first draft of this manuscript. BIE and PWA supervised the preparation of the manuscript and contributed to interpretation of the results. All authors approved the final manuscript and confirmed the responsibility of the content of this article.

Corresponding author

Correspondence to Paul W. Ackermann.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests regarding the publication of this paper.

Ethical approval

The Gothenburg Ethical Committee on Animal Research approved this study (Dnr. 257-2009).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silva, F.S., Abreu, B.J., Eriksson, B.I. et al. Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions. Knee Surg Sports Traumatol Arthrosc 29, 1990–1999 (2021). https://doi.org/10.1007/s00167-020-06239-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00167-020-06239-3

Keywords

Search

Navigation