Regenerative MRL/MpJ Tendon Cells Exhibit Sex Differences in Morphology, Proliferation, Mechanosensitivity, and Cell-ECM Organization.
Jason C MarvinMolly E BrakewoodMong Lung Steve PoonNelly Andarawis-PuriPublished in: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2023)
Clinical and animal studies have reported the influence of sex on the incidenceandprogression of tendinopathy, which results indisparate structural andbiomechanical outcomes.However, there remains a paucity in our understanding of the sex-specific biological mechanisms underlyingeffective 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 havepreviously shown that the scarless healing capacity ofMRL/MpJ patellar tendons is associated withsexuallydimorphic regulation of gene expression for pathways involved in fibrosis, cell migration, adhesion, and extracellular matrix (ECM) remodeling following an acute midsubstance injury.Thus, we hypothesizedthatMRL/MpJ scarless tendon healingis mediated by sex-specific and temporally distinct orchestration of cell-ECM interactions. Accordingly, the present study comparatively evaluatedMRL/MpJ tendon cellsontwo-dimensional (glass) and scaffoldplatforms to examine cell behavior under biochemical and topographicalcues associated with tendon homeostasis and healing. Female MRL/MpJ cells showed reduced2Dmigration and spreading area accompanied withenhanced mechanosensing,ECM alignment, and fibronectin-mediatedcell proliferationcompared 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 elicitedenhanced 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 resultsprovide insight into the cellular features conserved within the MRL/MpJ phenotype and potential sex-specific targets for the development of more equitable therapeutics. This article is protected by copyright. All rights reserved.
Keyphrases
- induced apoptosis
- extracellular matrix
- gene expression
- cell cycle arrest
- cell therapy
- stem cells
- cell migration
- oxidative stress
- endoplasmic reticulum stress
- hepatitis b virus
- adipose tissue
- intensive care unit
- atomic force microscopy
- anterior cruciate ligament reconstruction
- liver failure
- transcription factor
- pseudomonas aeruginosa
- rotator cuff
- insulin resistance
- staphylococcus aureus
- climate change
- cystic fibrosis
- metabolic syndrome
- mechanical ventilation
- tissue engineering
- liver fibrosis
- candida albicans