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.
Highlights
The periosteum is a thin, dense layer of connective tissue that surrounds bones and is crucial to cortical bone homeostasis and repair.[1,2] The periosteum contains poorly delineated skeletal precursor populations, which are anatomically separated into outer fibrous and inner cambium layers.[1,3,4] the periosteum houses cells with two principal cellular fates, the discrimination of these progenitor cell subpopulations remains a challenge
Using cell ablation studies in combination with fluorescence-activated cell sorting (FACS) purification and transplantation, we found that Platelet-derived growth factor receptor α (PDGFRα) reporter+ periosteal cells are a highly osteoblastogenic population responsible for the canonical functions of the periosteum during homeostasis and repair
DISCUSSION the periosteum is an inconspicuous bone-lining surface composed of cells with a fibroblastic morphology, an increasing body of evidence shows that functionally relevant cellular heterogeneity exists in this tissue compartment.[6,8,9,20,41,42]
Summary
The periosteum is a thin, dense layer of connective tissue that surrounds bones and is crucial to cortical bone homeostasis and repair.[1,2] The periosteum contains poorly delineated skeletal precursor populations, which are anatomically separated into outer fibrous and inner cambium layers.[1,3,4] the periosteum houses cells with two principal cellular fates (osteoblasts and chondroblasts), the discrimination of these progenitor cell subpopulations remains a challenge. PDGFPDGFRβ signaling induces stem cell proliferation, trafficking, and angiotropism and mediates callus formation during bone repair.[11]
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