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Regenerative MRL/MpJ tendon cells exhibit sex differences in morphology, proliferation, mechanosensitivity, and cell-ECM organization.

Authors :
Marvin JC
Brakewood ME
Poon MLS
Andarawis-Puri N
Source :
Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2023 Oct; Vol. 41 (10), pp. 2273-2286. Date of Electronic Publication: 2023 Apr 11.
Publication Year :
2023

Abstract

Clinical and animal studies have reported the influence of sex on the incidence and progression of tendinopathy, which results in disparate structural and biomechanical outcomes. However, there remains a paucity in our understanding of the sex-specific biological mechanisms underlying effective tendon healing. To overcome this hurdle, our group has investigated the impact of sex on tendon regeneration using the super-healer Murphy Roths Large (MRL/MpJ) mouse strain. We have previously shown that the scarless healing capacity of MRL/MpJ patellar tendons is associated with sexually dimorphic regulation of gene expression for pathways involved in fibrosis, cell migration, adhesion, and extracellular matrix (ECM) remodeling following an acute mid-substance injury. Thus, we hypothesized that MRL/MpJ scarless tendon healing is mediated by sex-specific and temporally distinct orchestration of cell-ECM interactions. Accordingly, the present study comparatively evaluated MRL/MpJ tendon cells on two-dimensional (2D; glass) and scaffold platforms to examine cell behavior under biochemical and topographical cues associated with tendon homeostasis and healing. Female MRL/MpJ cells showed reduced 2D migration and spreading area accompanied by enhanced mechanosensing, ECM alignment, and fibronectin-mediated cell proliferation compared to male MRL/MpJ cells. Interestingly, female MRL/MpJ cells cultured on isotropic scaffolds showed diminished cell-ECM organization compared to male MRL/MpJ cells. Lastly, MRL/MpJ cells elicited enhanced cytoskeletal elongation and alignment, ECM deposition and organization, and connexin 43-mediated intercellular communication compared to male B6 cells, regardless of culture condition or sex. These results provide insight into the cellular features conserved within the MRL/MpJ phenotype and potential sex-specific targets for the development of more equitable therapeutics.<br /> (© 2023 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1554-527X
Volume :
41
Issue :
10
Database :
MEDLINE
Journal :
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Publication Type :
Academic Journal
Accession number :
37004178
Full Text :
https://doi.org/10.1002/jor.25562