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Superior mechanical recovery in male and female MRL/MpJ tendons is associated with a unique genetic profile.

Authors
  • George, Nisha S1
  • Bell, Rebecca2
  • Paredes, J J3
  • Taub, Peter J1
  • Andarawis-Puri, Nelly2, 3, 4
  • 1 Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, New York.
  • 2 Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York.
  • 3 Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.
  • 4 Hospital for Special Surgery Research Division, New York, New York.
Type
Published Article
Journal
Journal of Orthopaedic Research®
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jun 01, 2021
Volume
39
Issue
6
Pages
1344–1354
Identifiers
DOI: 10.1002/jor.24705
PMID: 32352601
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Tendon ruptures heal by forming a mechanically inferior scar. We have shown that male Murphy Roths large (MRL/MpJ) mice exhibit improved tendon healing, suggesting that they can inform biological mechanisms that lead to effective tendon healing. As sex impacts healing, we assessed the effect of sex on tendon healing in MRL/MpJ and normal healer C57BL/6 (B6) mice and compared the associated biological environment with identify genes that may be integral to the improved healing outcome. We hypothesized that (a) male MRL/MpJ mice will heal with improved mechanical properties compared to females; and (b) that regenerative tendon healing will be associated with decreased fibrotic pathways, decreased inflammation, and increased activity of matrix metalloproteinases (MMPs). A midsubstance punch was introduced, and tendons were harvested after (a) 1 or 7 days for profiling of 84 genes; (b) 7 or 14 days for the assessment of MMP-2 and MMP-9 activity; and (c) 6 weeks for mechanical assessment. MRL/MpJ tendons healed with the better restoration of mechanical properties than B6 tendons. Sex did not affect the mechanical properties of healing B6 or MRL/MpJ tendons. Comparison of the gene expression profiles in the context of the mechanical outcome revealed several differences between MRL/MpJ and B6 tendon healing, including, lower inflammation, an earlier higher expression of TGF-β-related genes that diminish by 7 days, and genes associated with enhanced cell migration in MRL/MpJ in comparison to B6 tendons. We expect that the timecourse and expression levels of these genes in scarless MRL/MpJ tendon healing represent the balanced environment that leads to improved tendon healing. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.

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