AI Article Synopsis

  • Researchers studied MRL mice, a model for tissue regeneration, to investigate how tendons heal compared to C57 mice, finding that MRL tendons showed faster recovery and less scarring.
  • RNA sequencing revealed that different healing mechanisms were at play, with C57 mice exhibiting pathways linked to inflammation and fibrosis, while MRL mice showed a focus on cell cycle regulation.
  • Analysis of proteins in blood samples indicated that MRL mice had lower levels of certain inflammatory markers, suggesting that their unique healing processes could offer insights for enhancing tendon repair in humans.

Article Abstract

To better understand the molecular mechanisms of tendon healing, we investigated the Murphy Roth's 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. RNA-seq analysis revealed that differentially expressed genes in the C57 healing tendon at 7 days post injury were functionally linked to fibrosis, immune system signaling and extracellular matrix (ECM) organization, while the differentially expressed genes in the MRL injured tendon were dominated by cell cycle pathways. These gene expression changes were associated with increased α-SMA+ myofibroblast and F4/80+ macrophage activation and abundant BCL-2 expression in the C57 injured tendons. Transcriptional analysis of upstream regulators using Ingenuity Pathway Analysis showed positive enrichment of TGFB1 in both C57 and MRL healing tendons, but with different downstream transcriptional effects. MRL tendons exhibited of cell cycle regulatory genes, with negative enrichment of the cell senescence-related regulators, compared to the positively-enriched inflammatory and fibrotic (ECM organization) pathways in the C57 tendons. Serum cytokine analysis revealed decreased levels of circulating senescence-associated circulatory proteins 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 in MRL mice, and could give cues to improved tendon healing.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863792PMC
http://dx.doi.org/10.1038/s41598-022-07124-4DOI Listing

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