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

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.

Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice

“…8A), which is consistent with published studies. (31) We further confirmed these observations using FC and found that the proportion of the PDGFRα + cells in the nonhematopoietic and nonendothelial (CD45 À CD31 À ) population was $15-fold higher in the intact bone (devoid of BM) than in the BM (Fig. 8B).…”

“…injection of 100 mg/kg tamoxifen (Sigma-Aldrich) for 5 successive days; on the sixth day, the mice underwent the fracture surgeries. (31) At harvest time, the animal was euthanized, and the fractured hindlimb was harvested from the mid-femur to the tibiotalar joint to avoid disturbing the callus tissue. Most of the surrounding soft tissues were removed with care not to disturb the fracture site.…”

Acetabular Reaming Is a Reliable Model to Produce and Characterize Periarticular Heterotopic Ossification of the Hip

“… 42 Basal expression of PDGFRα reporter activity is present within multiple cells capable of bone formation, including perivascular adventitial cells, 26 perineural cells, 26 intra-articular, and periarticular ligaments, 27 and in some periosteal cells. 43 Interesting, in our prior work we observed that the frequency of PDGFRα + cells especially within the perivascular space differs somewhat widely across organs. 26 Some vascularized tissue sites are enriched for PDGFRα + adventitial perivascular cells (eg, aorta, skeletal muscle, and adipose tissue), while several visceral sites showed infrequent PDGFRα + adventitial cells (eg, liver and lung).…”

Chronological and Replicative Aging of CD51+/PDGFR-α+ Pulp Stromal Cells

“…In this study, we analyzed the CD51 + /PDGFR-α + population in pulp tissue and cultured cells. Previous studies reported that PDGFR-α + cells were increased in the bone marrow of aged mice, whereas PDGFR-α + cells were noted to be critical for bone formation (Maryanovich et al 2018; Xu et al 2022). The influence of chronological aging on PDGFR-α + cells and pulp tissue remains unclear.…”

“…In our study, the number of PDGFR-α + and CD51 + cells decreased during chronological senescence. PDGFR-α + cells have been reported to be stem cells/progenitor cells and play a role in tissue repair and regeneration (Maryanovich et al 2018; Xu et al 2022). We observed a decreased self-renewal ability of hDPSCs from aged human pulp.…”