Identification of Periosteal Osteogenic Progenitors in Jawbone

Abstract

Unlike long bones, jawbone development is mainly accomplished by intramembranous ossification resulting from the differentiation of periosteal progenitor cells. However, the spatiotemporal ontogeny of periosteal progenitor cells during jawbone development and repair remains elusive. In this study, we mapped the transcriptional landscape of the human jawbone periosteum at single-cell resolution and identified a cathepsin K (Ctsk)+ periosteal subset. Lineage tracing analysis indicated that Ctsk-Cre–labeled periosteal cells could make contributions to jawbone development. However, different from the periosteal-specific location of Ctsk+ cells in long bone, we also identified Ctsk+ stromal cells in jawbone marrow and implied the heterogeneity of jawbone Ctsk+ hierarchy. In further analysis of the periosteal progenitor cell subset of heterogeneous Ctsk+ hierarchy, we identified a unique Ctsk+Ly6a+ subset of cells. The additional marker Ly6a helped to further confine the progenitor subset to the jawbone periosteum and was nearly undetectable in the bone marrow. Defects in the jawbone could activate the migration and osteogenic differentiation of Ctsk+Ly6a+ cells. Local ablation of Ctsk+ cells by diphtheria reduced the number of Ctsk+Ly6a+ cells and delayed the repair of the bone defect. Taken together, we identify a novel periosteal osteogenic progenitor subset that is active in jawbone osteogenesis and healing.

Insights into skeletal stem cells

“…3 ). 192 The periosteum SSCs are regulated by schwann cells in a paracrine manner. 193 Myelin PLP + schwann cells played a role in tissue repair.…”

Guided bone regeneration for peri‐implant augmentation: A retrospective study comparing two surgical techniques with a mean follow‐up of 26 months

“…The prominent osteogenic capability of the periosteum may play a key role in bone regeneration. The inner cambium layer of the periosteum contains a variety of bone cells, such as periosteum‐derived stem cells, osteoprogenitor cells, and osteoblasts (Zhang et al., 2022), which have been proven to contribute to bone formation and fracture healing (Debnath et al., 2018; Ding et al., 2022; Duchamp de Lageneste et al., 2018). Additionally, animal experiments have indicated that bone regeneration is induced after periosteal elevation using implants (Lutz et al., 2017) or scaffold materials (Mouraret et al., 2014).…”

Endochondral Repair of Jawbone Defects Using Periosteal Cell Spheroids

“…It was recently reported that human jawbone periosteum can be easily accessed during maxillofacial surgeries, providing convenience for cell isolation (Ding et al 2022). Furthermore, periosteal cells from jawbone possess specific progenitor subsets active in jawbone development and defect healing (Ding et al 2022). Specifically, the mandible-derived periosteal cells were shown excellent potentials in both in vitro and in vivo chondrogenic and osteogenic differentiation potential (Groeneveldt et al 2020).…”

“…However, the jawbone periosteal cells currently are understudied. It was recently reported that human jawbone periosteum can be easily accessed during maxillofacial surgeries, providing convenience for cell isolation (Ding et al 2022). Furthermore, periosteal cells from jawbone possess specific progenitor subsets active in jawbone development and defect healing (Ding et al 2022).…”

“…Specifically, a segmental jawbone defect has been primarily healed via endochondral ossification, in which a cartilaginous “soft callus” occurs in the center of the defect and is eventually replaced by bone (Wong et al 2021; Marcucio et al 2023). A previous study has shown that most cells forming the “soft callus” during mandibular fracture healing are derived from the periosteum (Leucht et al 2008), and the latter represents promising skeletal stem cell sources to repair bone defects (Ding et al 2022). Hence, developing a jawbone periosteum-derived cell (jb-PDC)–based strategy using “endochondral ossification” represents a promising therapeutic modality to repair jawbone defects (Kruijt Spanjer et al 2017; Marcucio et al 2023).…”