Proteins Derived From MRL/MpJ Tendon Provisional Extracellular Matrix and Secretome Promote Pro-Regenerative Tenocyte Behavior.

Autor: Marvin JC, Liu EJ, Chen HH, Shiovitz DA, Andarawis-Puri N
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 11. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1101/2024.07.08.602500
Abstrakt: Tendinopathies are prevalent musculoskeletal conditions that have no effective therapies to attenuate scar formation. In contrast to other adult mammals, the tendons of Murphy Roths Large (MRL/MpJ) mice possess a superior healing capacity following acute and overuse injuries. Here, we hypothesized that the application of biological cues derived from the local MRL/MpJ tendon environment would direct otherwise scar-mediated tenocytes towards a pro-regenerative MRL/MpJ-like phenotype. We identified soluble factors enriched in the secretome of MRL/MpJ tenocytes using bioreactor systems and quantitative proteomics. We then demonstrated that the combined administration of structural and soluble constituents isolated from decellularized MRL/MpJ tendon provisional ECM (dPECM) and the secretome stimulate scar-mediated rodent tenocytes towards enhanced mechanosensitivity, proliferation, intercellular communication, and ECM deposition associated with MRL/MpJ cell behavior. Our findings highlight key biological mechanisms that drive MRL/MpJ tenocyte activity and their interspecies utility to be harnessed for therapeutic strategies that promote pro-regenerative healing outcomes.
Teaser: Proteins enriched in a super-healer mouse strain elicit interspecies utility in promoting pro-regenerative tenocyte behavior.
Databáze: MEDLINE