Tenotomized Achilles tendons of MRL/MpJ mice show scar-mediated healing, but have superior recovery of biomechanical properties

Tang, N.; Wilson, K.; Weldemarian, M. M.; Tian, H.; Hart, C. D.; Rammath, P.; Sivalingam, D. S.; Glazier, J.; Jiang, J.; Leong, N.; Lowe, T.; Kane, M. A.; Iwamoto, M.; Kuo, C. K.; Enomoto-Iwamoto, M.

doi:10.1101/2025.05.13.653102

bioRxiv · 10.1101/2025.05.13.653102

Tenotomized Achilles tendons of MRL/MpJ mice show scar-mediated healing, but have superior recovery of biomechanical properties

Tang, N.·Wilson, K.·Weldemarian, M. M.·Tian, H.·Hart, C. D.·Rammath, P.·Sivalingam, D. S.·Glazier, J.·Jiang, J.·Leong, N.·Lowe, T.·Kane, M. A.·Iwamoto, M.·Kuo, C. K.·Enomoto-Iwamoto, M.

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Abstract

Tendon healing in Murphy Ross Large (MRL/MpJ) mice was examined using an Achilles tendon tenotomy model, a full transection model, compared to a patella focal injury model in which tendons in MRL/MpJ mice showed regenerative healing. After complete transection, the Achilles tendons of MRL/MpJ mice healed via scar formation, regardless of sex, as did C57BL/6J mice. Tensile testing found that mechanical properties of injured tendons of both MRL/MpJ female and male mice exhibited comparable levels to those of C57BL/6J female and male mice, respectively after 4 weeks of healing, which is during the remodeling phase. After 10 weeks of healing, injured tendons of MRL/MpJ mice possessed smaller heterotopic ossification volumes than those of C57BL/6J mice. Proteomics analysis revealed similar alterations to signaling pathways in injured tendons of MRL/MpJ and C57BL/6J male mice after 4 weeks of healing. However, among the altered pathways, actin cytoskeleton and integrin signaling pathways were two of the top pathways that were more prominently activated in C57BL/6J males than in MRL/MpJ males. These findings indicate that MRL/MpJ mice possess limited capacity to regenerate injured tendons after complete rupture, and that tenotomized Achilles tendons of MRL/MpJ male mice have lesser induction of heterotopic ossification and lower activation of the signaling pathways also induced with injury in C57BL/6J male mice.

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Tang, N., Wilson, K., Weldemarian, M. M., Tian, H., Hart, C. D., Rammath, P., Sivalingam, D. S., Glazier, J., Jiang, J., Leong, N., Lowe, T., Kane, M. A., Iwamoto, M., Kuo, C. K., Enomoto-Iwamoto, M.. 2025-05-16. Tenotomized Achilles tendons of MRL/MpJ mice show scar-mediated healing, but have superior recovery of biomechanical properties. https://doi.org/10.1101/2025.05.13.653102

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