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. 2023 Oct;41(10):2273-2286.
doi: 10.1002/jor.25562. Epub 2023 Apr 11.

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

Jason C Marvin  1 , Molly E Brakewood  1 , Mong L S Poon  2 , Nelly Andarawis-Puri  2   3
Affiliations
Free article

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

Jason C Marvin et al. J Orthop Res. 2023 Oct.
Free article

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.

Keywords: cell biology; extracellular matrix; regeneration; scaffold; tendon.

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References

REFERENCES

    1. Screen HRC, Berk DE, Kadler KE, Ramirez F, Young MF. Tendon functional extracellular matrix. J Orthop Res. 2015;33(6):793-799. doi:10.1002/jor.22818
    1. Freedman BR, Rodriguez AB, Leiphart RJ, et al. Dynamic loading and tendon healing affect multiscale tendon properties and ECM stress transmission. Sci Rep. 2018;8(1):10854. doi:10.1038/s41598-018-29060-y
    1. Chatterjee M, Muljadi PM, Andarawis-Puri N. The role of the tendon ECM in mechanotransduction: disruption and repair following overuse. Connect Tissue Res. 2022;63(1):28-42. doi:10.1080/03008207.2021.1925663
    1. Galatz LM, Gerstenfeld L, Heber-Katz E, Rodeo SA. Tendon regeneration and scar formation: the concept of scarless healing. J Orthop Res. 2015;33(6):823-831. doi:10.1002/jor.22853
    1. Andarawis-Puri N, Flatow EL, Soslowsky LJ. Tendon basic science: development, repair, regeneration, and healing. J Orthop Res. 2015;33(6):780-784. doi:10.1002/jor.22869

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