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The Tendon Injury Response is Influenced by Decorin and Biglycan

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Abstract

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.

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Acknowledgments

This study was funded by NIH Grant 5R01AR055543 and the Penn Center for Musculoskeletal Disorders (NIH, P30 AR050950). None of the authors have any conflicts of interest to report. We acknowledge Benjamin Freedman for valuable discussions.

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Authors and Affiliations

  1. The McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA, 19104, USA

    Andrew A. Dunkman, Mark R. Buckley, Stephen J. Thomas, Lauren Satchell, Akash Kumar, Lydia Pathmanathan, David P. Beason & Louis J. Soslowsky

  2. Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 8, Tampa, FL, 33612, USA

    Michael J. Mienaltowski, Sheila M. Adams & David E. Birk

  3. Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Street, Jefferson Alumni Hall, Suite 249, Philadelphia, PA, 19107, USA

    Renato V. Iozzo

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  1. Andrew A. Dunkman
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Correspondence to Louis J. Soslowsky.

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Associate Editor Eric M. Darling oversaw the review of this article.

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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

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

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

Supplementary material 4 (LNK 0 kb) S-Fig. 3. A prepared tendon undergoing mechanical testing

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Dunkman, A.A., Buckley, M.R., Mienaltowski, M.J. et al. The Tendon Injury Response is Influenced by Decorin and Biglycan. Ann Biomed Eng 42, 619–630 (2014). https://doi.org/10.1007/s10439-013-0915-2

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  • DOI: https://doi.org/10.1007/s10439-013-0915-2

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