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


Journal

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726

Informations de publication

Date de publication:
06 2021
Historique:
revised: 22 04 2020
received: 15 10 2019
accepted: 24 04 2020
pubmed: 1 5 2020
medline: 3 9 2021
entrez: 1 5 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32352601
doi: 10.1002/jor.24705
pmc: PMC7606617
mid: NIHMS1611978
doi:

Substances chimiques

Matrix Metalloproteinase 2 EC 3.4.24.24
Matrix Metalloproteinase 9 EC 3.4.24.35

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1344-1354

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR052743
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR068301
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR068301
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR52743
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR068301
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR52743
Pays : United States

Informations de copyright

© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.

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Auteurs

Nisha S George (NS)

Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, New York.

Rebecca Bell (R)

Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York.

J J Paredes (JJ)

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.

Peter J Taub (PJ)

Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, New York.

Nelly Andarawis-Puri (N)

Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York.
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.
Hospital for Special Surgery Research Division, New York, New York.

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