Annals of Biomedical Engineering

, Volume 42, Issue 3, pp 619–630

The Tendon Injury Response is Influenced by Decorin and Biglycan

  • Andrew A. Dunkman
  • Mark R. Buckley
  • Michael J. Mienaltowski
  • Sheila M. Adams
  • Stephen J. Thomas
  • Lauren Satchell
  • Akash Kumar
  • Lydia Pathmanathan
  • David P. Beason
  • Renato V. Iozzo
  • David E. Birk
  • Louis J. Soslowsky


Defining the constituent regulatory molecules in tendon is critical to understanding the process of tendon repair and instructive to the development of novel treatment modalities. The purpose of this study is to define the structural, expressional, and mechanical changes in the tendon injury response, and elucidate the roles of two class I small leucine-rich proteoglycans (SLRPs). We utilized biglycan-null, decorin-null and wild type mice with an established patellar tendon injury model. Mechanical testing demonstrated functional changes associated with injury and the incomplete recapitulation of mechanical properties after 6 weeks. In addition, SLRP deficiency influenced the mechanical properties with a marked lack of improvement between 3 and 6 weeks in decorin-null tendons. Morphological analyses of the injury response and role of SLRPs demonstrated alterations in cell density and shape as well as collagen alignment and fibril structure resulting from injury. SLRP gene expression was studied using RT-qPCR with alterations in expression associated with the injured tendons. Our results show that in the absence of biglycan initial healing may be impaired while in the absence of decorin later healing is clearly diminished. This suggests that biglycan and decorin may have sequential roles in the tendon response to injury.


Tendon Injury Biglycan Decorin Proteoglycan Extracellular matrix SLRP Healing 

Supplementary material

10439_2013_915_MOESM1_ESM.pdf (256 kb)
Supplementary material 1 (PDF 256 kb) S-Table 1. RT-qPCR: Mean Ct numbers and mean plate efficiencies, raw data
10439_2013_915_MOESM2_ESM.lnk (1 kb)
Supplementary material 2 (LNK 0 kb) S-Fig. 1. Mean dynamic modulus and mean tanδ for each genotype at each tested strain and frequency. Note the increasing spread between 3 weeks and 6 weeks in WT and Bgn−/− (but not Dcn/) as strain increases. Seemingly, remodeling is more influential at these higher strains. See Figs. 1 and 2 for representative error bars; Table 1 and Table 2 for statistics
10439_2013_915_MOESM3_ESM.lnk (1 kb)
Supplementary material 3 (LNK 0 kb) S-Fig. 2. Quasi-static properties from ramp to failure and p-values from t tests. (a) toe modulus. (b) linear modulus. (c) transition strain (d) transition stress
10439_2013_915_MOESM4_ESM.lnk (1 kb)
Supplementary material 4 (LNK 0 kb) S-Fig. 3. A prepared tendon undergoing mechanical testing


  1. 1.
    Ameye, L., D. Aria, K. Jepsen, A. Oldberg, T. Xu, and M. F. Young. Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J. 6:673–680, 2002.CrossRefGoogle Scholar
  2. 2.
    Ansorge, H. L., S. Adams, D. E. Birk, and L. J. Soslowsky. Mechanical, compositional, and structural properties of the post-natal mouse Achilles tendon. Ann. Biomed. Eng. 39:1904–1913, 2011.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ansorge, H. L., S. Adams, A. F. Jawad, D. E. Birk, and L. J. Soslowsky. Mechanical property changes during neonatal development and healing using a multiple regression model. J. Biomech. 45:1288–1292, 2012.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Berglund, M., C. Reno, D. A. Hart, and M. Wiig. Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath. J. Hand Surg. Am. 31:1279–1287, 2006.PubMedCrossRefGoogle Scholar
  5. 5.
    Birk, D. E., and P. Bruckner. Collagen suprastructures. In: Topics in Current Chemistry: Collagen, edited by J. Brinckmann, P. K. Müller, and H. Notbohm. Berlin: Springer-Verlag, 247:185–205, 2005.Google Scholar
  6. 6.
    Birk, D. E., M. V. Nurminskaya, and E. I. Zycband. Collagen fibrillogenesis in situ: fibril segments undergo post-depositional modifications resulting in linear and lateral growth during matrix development. Dev. Dyn. 202:229–243, 1995.PubMedCrossRefGoogle Scholar
  7. 7.
    Buckley, M. R., A. A. Dunkman, K. E. Reuther, A. Kumar, L. Pathmanathan, D. P. Beason, D. E. Birk, and L. J. Soslowsky. Validation of an empirical damage model for aging and in vivo injury of the murine patellar tendon. J. Biomech. Eng. 135:041005-1-7.Google Scholar
  8. 8.
    Chen, S., and D. E. Birk. 2013 The regulatory roles of small leucine-rich proteoglycans in extracellular assembly. FEBS J. 2013: 10.1111/febs.12136.
  9. 9.
    Connizzo, B. K., J. J. Sarver, D. E. Birk, and L. J. Soslowsky. Effect of age and proteoglycan deficiency on collagen fiber re-alignment and mechanical properties in mouse supraspinatus tendon. J. Biomech. Eng. 135(2):021019, 2013.PubMedCrossRefGoogle Scholar
  10. 10.
    Corsi, A., T. Xu, X. D. Chen, A. Boyde, J. Liang, M. Mankani, B. Sommer, R. V. Iozzo, I. Eichstetter, P. G. Robey, P. Bianco, and M. F. Young. Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. J. Bone Miner. Res. 17:1180–1189, 2002.PubMedCrossRefGoogle Scholar
  11. 11.
    Dafforn, A., P. Chen, G. Deng, M. Herrler, D. Iglehart, S. Koritala, S. Lato, S. Pillarisetty, R. Purohit, M. Wang, S. Wang, and N. Kurn. Linear mRNA amplification from as little as 5 ng total RNA for global gene expression analysis. Biotechniques 37:854–857, 2004.PubMedGoogle Scholar
  12. 12.
    Dourte, L. M., L. Pathmanathan, A. F. Jawad, R. V. Iozzo, M. J. Mienaltowski, D. E. Birk, and L. J. Soslowsky. Influence of decorin on the mechanical, compositional, and structural properties of the mouse patellar tendon. J. Biomech. 134(3):031005, 2012.CrossRefGoogle Scholar
  13. 13.
    Dunkman, A. A., M. R. Buckley, M. J. Mienaltowski, A. Kumar, D. P. Beason, L. Pathmanathan, L. D. E. Birk, and L. J. Soslowsky. 2013. Dynamic mechanical properties of tendon repair tissue are unaffected by aging. Trans. Orthop. Res. Soc. 38:614.Google Scholar
  14. 14.
    Dunkman, A. A., M. R. Buckley, M. J. Mienaltowski, S. M. Adams, S. J. Thomas, L. Satchell, A. Kumar, L. Pathmanathan, D. P. Beason, R. V. Iozzo, D. E. Birk, and L. J. Soslowsky. Decorin expression is required for age-related changes in tendon structure and mechanical properties. Matrix Biol. 32:3–13, 2013.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Ezura, Y., S. Chakravarti, A. Oldberg, I. Chervoneva, and D. E. Birk. Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons. J. Cell Biol. 151:779–788, 2000.PubMedCrossRefGoogle Scholar
  16. 16.
    Favata, M. Scarless healing in the fetus: Implications and strategies for postnatal tendon repair. Dissertation available from ProQuest. Paper AAI3246156, 2006.Google Scholar
  17. 17.
    Iozzo, R. V. The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J. Biol. Chem. 274:18843–18846, 1999.PubMedCrossRefGoogle Scholar
  18. 18.
    Kumar, A., A. A. Dunkman, M. R. Buckley, L. Pathmanathan, M. J. Mienaltowski, D. P. Beason, R. V. Iozzo, D. E. Birk, and L. J. Soslowsky. Tendon repair response to injury is affected by the absence of biglycan and decorin. Trans. Orthop. Res. Soc. 37:158, 2012.Google Scholar
  19. 19.
    Leadbetter, W. B. Cell-matrix response in tendon injury. Clin. Sports Med. 11:533–578, 1992.PubMedGoogle Scholar
  20. 20.
    Lin, T. W., L. Cardenas, D. L. Glaser, and L. J. Soslowsky. Tendon healing in interleukin-4 and interleukin-6 knockout mice. J. Biomech. 39:61–69, 2006.PubMedCrossRefGoogle Scholar
  21. 21.
    Lui, P. P., Y. C. Cheuk, Y. W. Lee, and K. M. Chan. Ectopic chondro-ossification and erroneous extracellular matrix deposition in a tendon window injury model. J. Orthop. Res. 301:37–46, 2012.CrossRefGoogle Scholar
  22. 22.
    Lujan, T. J., C. J. Underwood, N. T. Jacobs, and J. A. Weiss. Contribution of glycosaminoglycans to viscoelastic tensile behavior of human ligament. J. Appl. Physiol. 106:423–431, 2009.PubMedCrossRefGoogle Scholar
  23. 23.
    Ramakers, C., J. M. Ruijter, R. H. Deprez, and A. F. Moorman. Assumption-free analysis of quantitative realtime polymerase chain reaction (PCR) data. Neurosci. Lett. 339, 62–66, 2003.Google Scholar
  24. 24.
    Reed, C. C., and R. V. Iozzo. The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconj. J. 19:249–255, 2002.PubMedCrossRefGoogle Scholar
  25. 25.
    Rühland, C., E. Schönherr, H. Robenek, U. Hansen, R. V. Iozzo, P. Bruckner, and D. G. Seidler. The glycosaminoglycan chain of decorin plays an important role in collagen fibril formation at the early stages of fibrillogenesis. FEBS J. 274:4246–4255, 2007.PubMedCrossRefGoogle Scholar
  26. 26.
    Schefe, J. H., K. E. Lehmann, I. R. Buschmann, T. Unger, and H. Funke-Kaiser. Quantitative real-time RT-PCR data analysis: current concepts and the novel “gene expression’s CT difference” formula. J. Mol. Med. 84:901–910, 2006.PubMedCrossRefGoogle Scholar
  27. 27.
    Young, M. F., Y. Bi, L. Ameye, and X. D. Chen. Biglycan knockout mice: new models for musculoskeletal diseases. Glycoconj. J. 19:257–262, 2002.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang, G., S. Chen, S. Goldoni, B. W. Calder, H. C. Simpson, R. T. Owens, D. J. McQuillan, M. F. Young, R. V. Iozzo, and D. E. Birk. Genetic evidence for the coordinated regulation of collagen fibrillogenesis in the cornea by decorin and biglycan. J. Biol. Chem. 284:8888–8897, 2009.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang, G., Y. Ezura, I. Chervoneva, P. S. Robinson, D. P. Beason, E. T. Carine, L. J. Soslowsky, R. V. Iozzo, and D. E. Birk. Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development. J. Cell. Biochem. 98:1436–1449, 2006.PubMedCrossRefGoogle Scholar
  30. 30.
    Zhang, G., B. B. Young, Y. Ezura, M. Favata, L. J. Soslowsky, S. Chakravarti, and D. E. Birk. Development of tendon structure and function: regulation of collagen fibrillogenesis. J. Musculoskeletal. Neuronal. Interact. 5:5–21, 2005.Google Scholar

Copyright information

© Biomedical Engineering Society 2013

Authors and Affiliations

  • Andrew A. Dunkman
    • 1
  • Mark R. Buckley
    • 1
  • Michael J. Mienaltowski
    • 2
  • Sheila M. Adams
    • 2
  • Stephen J. Thomas
    • 1
  • Lauren Satchell
    • 1
  • Akash Kumar
    • 1
  • Lydia Pathmanathan
    • 1
  • David P. Beason
    • 1
  • Renato V. Iozzo
    • 3
  • David E. Birk
    • 2
  • Louis J. Soslowsky
    • 1
  1. 1.The McKay Orthopaedic Research LaboratoryUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Molecular Pharmacology & Physiology, Morsani College of MedicineUniversity of South FloridaTampaUSA
  3. 3.Department of Pathology, Anatomy & Cell BiologyThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations