Uncorrelated Healing Response of Tendon and Ear Injuries in MRL Highlight a Role for the Local Tendon Environment in Driving Scarless Healing

Overview

Journal Connect Tissue Res

Publisher Informa Healthcare

Date 2018 Jun 23

PMID 29929396

Citations 13

Authors

Juan Paredes

David A Shiovitz

Nelly Andarawis-Puri

Affiliations

Soon will be listed here.

Abstract

Purpose: Tendon tears are common injuries that heal with scar formation. Interestingly, MRL/MpJ mice heal without scar in several tissues, including tendon. Most hypotheses regarding scarless healing implicate the systemic environment. However, the tissue-specificity of this regenerative response and our previous findings showing regeneration of sub-rupture tendon injuries, which lack an overt systemic response, motivate a tissue-driven hypothesis. Our objective is to investigate the potential of the local tendon environment in driving scarless healing (1) by comparing the systemic response and the healing capacity associated with ear and tendon injuries in MRL/MpJ mice, and (2) by comparing intrinsic healing properties between MRL/MpJ and normal healer C57Bl/6 tendons.

Methods: We examined the systemic inflammatory and local structural environments of ear and tendon punch injuries in MRL/MpJ and C57Bl/6 mice. Systemic differences were analyzed to assess effects of different injuries on the inflammatory response. Correlations were assessed between MRL/MpJ ear and tendon injuries to compare the extent of healing between regenerative tissues.

Results: Analysis showed similarities between the systemic environment in MRL/MpJ post ear or tendon injuries. However, comparable inflammatory responses did not translate into analogous healing between tissues, suggesting that the systemic environment is not the driver of regeneration. Supporting the regenerative role of the local environment, healing MRL/MpJ tendons exhibited improved matrix and cell alignment and a distinct composition of growth factors and Hyaluronan from C57Bl/6.

Conclusion: These findings support the tissue-driven hypothesis for MRL/MpJ tendon regeneration and motivate further investigation regarding specific roles of extracellular factors in scarless healing.

Citing Articles

The superior healing capacity of MRL tendons is minimally influenced by the systemic environment of the MRL mouse.

Frankewycz B, Bell R, Chatterjee M, Andarawis-Puri N Sci Rep. 2023; 13(1):17242.

PMID: 37821476 PMC: 10567747. DOI: 10.1038/s41598-023-42449-8.

Earlier proteoglycan turnover promotes higher efficiency matrix remodeling in MRL/MpJ tendons.

Aggouras A, Connizzo B J Orthop Res. 2023; 41(10):2261-2272.

PMID: 36866831 PMC: 10475140. DOI: 10.1002/jor.25542.

Detergent-Free Decellularization Preserves the Mechanical and Biological Integrity of Murine Tendon.

Marvin J, Mochida A, Paredes J, Vaughn B, Andarawis-Puri N Tissue Eng Part C Methods. 2022; 28(12):646-655.

PMID: 36326204 PMC: 9807253. DOI: 10.1089/ten.TEC.2022.0135.

Macrophage-mediated PDGF Activation Correlates With Regenerative Outcomes Following Musculoskeletal Trauma.

Chowdary A, Maerz T, Henn D, Hankenson K, Pagani C, Marini S Ann Surg. 2022; 278(2):e349-e359.

PMID: 36111847 PMC: 10014496. DOI: 10.1097/SLA.0000000000005704.

Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse.

Kallenbach J, Freeberg M, Abplanalp D, Alenchery R, Ajalik R, Muscat S Sci Rep. 2022; 12(1):3026.

PMID: 35194136 PMC: 8863792. DOI: 10.1038/s41598-022-07124-4.

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