Heterogeneity of murine periosteum progenitors involved in fracture healing
- University of Auckland, New Zealand
- University of Connecticut, United States
- University of Zagreb, Croatia
Abstract
The periosteum is the major source of cells involved in fracture healing. We sought to characterize progenitor cells and their contribution to bone fracture healing. The periosteum is highly enriched for progenitor cells, including Sca1+ cells, CFU-F and label-retaining cells compared to the endosteum and bone marrow. Using lineage tracing, we demonstrate that αSMA identifies long-term, slow-cycling, self-renewing osteochondroprogenitors in the adult periosteum that are functionally important for bone formation during fracture healing. In addition, Col2.3CreER-labeled osteoblast cells contribute around 10% of osteoblasts, but no chondrocytes in fracture calluses. Most periosteal osteochondroprogenitors following fracture, can be targeted by αSMACreER. Previously identified skeletal stem cell populations were common in periosteum, but contained high proportions of mature osteoblasts. We have demonstrated that the periosteum is highly enriched for skeletal progenitor cells and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.
Data availability
RNAseq data have been deposited in GEO under accession GSE165846. Source data files are provided for all figures (1-8)
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scRNAseq of aSMACreER/Ai9+ periosteum cellsNCBI Gene Expression Omnibus, GSE165846.
Article and author information
Author details
Funding
Connecticut Innovations (14-SCA-UCHC-02)
- Brya G Matthews
Health Research Council of New Zealand (Sir Charles Hercus Fellowship)
- Brya G Matthews
American Society for Bone and Mineral Research (Rising Star Award)
- Brya G Matthews
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR055607)
- Ivo Kalajzic
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR070813)
- Ivo Kalajzic
Connecticut Innovations (16-RMB-UCHC-10)
- Ivo Kalajzic
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Subburaman Mohan, Loma Linda University, United States
Ethics
Animal experimentation: The majority of the study was performed at UConn Health in an AAALAC accredited facility in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Studies were approved by the UConn Health institutional animal care and use committee (IACUC) under protocol numbers 100490-0815, 101095-0518, 101757-0221 and Hz#-Dox0322e-101058 and Hz#-MCh0331e-101086. Experiments at the University of Auckland were performed in accordance with the University of Auckland Code of Ethical Conduct (CEC) and the Animal Welfare Act 1999, under Animal Ethical Committee approval 001940.
Version history
- Received: May 4, 2020
- Accepted: February 8, 2021
- Accepted Manuscript published: February 9, 2021 (version 1)
- Version of Record published: February 25, 2021 (version 2)
Copyright
© 2021, Matthews 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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Heterogeneity of murine periosteum progenitors involved in fracture healing
eLife 10:e58534.
https://doi.org/10.7554/eLife.58534
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