Scleraxis-lineage cells are required for tendon homeostasis and their depletion induces an accelerated extracellular matrix aging phenotype
- University of Rochester Medical Center, United States
Abstract
Aged tendons have disrupted homeostasis, increased injury risk, and impaired healing capacity. Understanding mechanisms of homeostatic disruption is crucial for developing therapeutics to retain tendon health through the lifespan. Here, we developed a novel model of accelerated tendon extracellular matrix (ECM) aging via depletion of Scleraxis-lineage cells in young mice (Scx-DTR). Scx-DTR recapitulates many aspects of tendon aging including comparable declines in cellularity, alterations in ECM structure, organization, and composition. Single cell RNA sequencing demonstrated a conserved decline in tenocytes associated with ECM biosynthesis in aged and Scx-DTR tendons, identifying the requirement for Scleraxis-lineage cells during homeostasis. However, the remaining cells in aged and Scx-DTR tendons demonstrate functional divergence. Aged tenocytes become pro-inflammatory and lose proteostasis. In contrast, tenocytes from Scx-DTR tendons demonstrate enhanced remodeling capacity. Collectively, this study defines Scx-DTR as a novel model of accelerated tendon ECM aging and identifies novel biological intervention points to maintain tendon function through the lifespan.
Data availability
Single cell RNA sequencing data has been deposited at Gene Expression Omnibus (GEO) (Accession # GSE214929) and are publicly available as of the date of publication. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE 38 partner repository with the dataset identifier PXD037230.
Article and author information
Author details
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR073169)
- Alayna E Loiselle
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR077527)
- Alayna E Loiselle
National Institute of Arthritis and Musculoskeletal and Skin Diseases (K99 AR080757)
- Anne EC Nichols
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mei Wan, Johns Hopkins University, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal studies were approved by the University Committee for Animal Resources (UCAR) (protocol 2014-004E)
Version history
- Preprint posted: January 21, 2022 (view preprint)
- Received: October 13, 2022
- Accepted: January 18, 2023
- Accepted Manuscript published: January 19, 2023 (version 1)
- Version of Record published: February 8, 2023 (version 2)
- Version of Record updated: January 3, 2024 (version 3)
Copyright
© 2023, Korcari et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Scleraxis-lineage cells are required for tendon homeostasis and their depletion induces an accelerated extracellular matrix aging phenotype
eLife 12:e84194.
https://doi.org/10.7554/eLife.84194
Further reading
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