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Original Article | Open Access

PDGFRα reporter activity identifies periosteal progenitor cells critical for bone formation and fracture repair

Jiajia Xu1,, Yiyun Wang1,, Zhu Li2, Ye Tian1,3, Zhao Li1, Amy Lu1, Ching-Yun Hsu1, Stefano Negri1, Cammy Tang1, Robert J. Tower2, Carol Morris2, Aaron W. James1 ( )
Departments of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
Departments of Orthopedics, Johns Hopkins University, Baltimore, MD 21205, USA
Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, PR China

These authors contributed equally: Jiajia Xu, Yiyun Wang

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Abstract

The outer coverings of the skeleton, which is also known as the periosteum, are arranged in concentric layers and act as a reservoir for tissue-specific bone progenitors. The cellular heterogeneity within this tissue depot is being increasingly recognized. Here, inducible PDGFRα reporter animals were found to mark a population of cells within the periosteum that act as a stem cell reservoir for periosteal appositional bone formation and fracture repair. During these processes, PDGFRα reporter+ progenitors give rise to Nestin+ periosteal cells before becoming osteoblasts and osteocytes. The diphtheria toxin-mediated ablation of PDGFRα reporter+ cells led to deficits in cortical bone formation during homeostasis and a diminutive hard callus during fracture repair. After ossicle transplantation, both mouse PDGFRα reporter+ periosteal cells and human Pdgfrα+ periosteal progenitors expand, ossify, and recruit marrow to a greater extent than their counterpart periosteal cells, whereas PDGFRα reporter− periosteal cells exhibit a predisposition to chondrogenesis in vitro. Total RNA sequencing identified enrichment of the secreted factors Fermt3 and Ptpn6 within PDGFRα reporter+ periosteal cells, which partly underlie the osteoblastogenic features of this cell population.

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Bone Research
Volume 10,
December 2022
Article number: 7
DOI: 10.1038/s41413-021-00176-8
Cite this article:
Xu J, Wang Y, Li Z, et al. PDGFRα reporter activity identifies periosteal progenitor cells critical for bone formation and fracture repair. Bone Research, 2022, 10: 7. https://doi.org/10.1038/s41413-021-00176-8

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Received: 13 October 2020
Revised: 13 July 2021
Accepted: 07 September 2021
Published: 25 January 2022
© The Author(s) 2022

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