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bioRxiv · 10.1101/2021.02.08.430308

Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse

Kallenbach, J.·Freeberg, M.·Abplanalp, D.·Lillis, J.·Ashton, J.·Loiselle, A. E.·Buckley, M.·van Wijnen, A.·Awad, H. A.
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Abstract

To better understand the molecular mechanisms of tendon healing, we investigated the Murphy Roths Large (MRL) mouse, which is considered a model of mammalian tissue regeneration. We show that compared to C57Bl/6J (C57) mice, injured MRL tendons have reduced fibrotic adhesions and cellular proliferation, with accelerated improvements in biomechanical properties. Transcriptional analysis of biological drivers showed positive enrichment of TGFB1 in both C57 and MRL healing tendons. However, only MRL tendons exhibited downstream transcriptional effects of cell cycle regulatory genes, with negative enrichment of the cell senescence-related regulators, compared to the positively-enriched inflammatory and ECM organization pathways in the C57 tendons. Serum cytokine analysis revealed decreased levels of circulating senescence-associated circulatory proteins (SASP) in response to injury in the MRL mice compared to the C57 mice. These data collectively demonstrate altered TGFB1 regulated inflammatory, fibrosis, and cell cycle pathways in flexor tendon repair.

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Kallenbach, J., Freeberg, M., Abplanalp, D., Lillis, J., Ashton, J., Loiselle, A. E., Buckley, M., van Wijnen, A., Awad, H. A.. 2021-02-08. Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse. https://doi.org/10.1101/2021.02.08.430308

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