Spp1 secreted by macrophages impairs osteogenic ability of Ctsk⁺Fmod⁺periosteal cells in jaw bone

Abstract

Periosteum, which covers the surface of most bones, mediates bone regeneration through endochondral ossification during fracture repair and intramembranous ossification under steady state. Periosteal cells (PCs) of jaw bones are different from those of long bones in phenotypic characteristics and functions. So far, the role of periosteum in jaw bones during bone grafting remain unclarified. Here we propose a subperiosteal bone grafting model based on the clinical procedures. By integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic (ST), we found a functional Ctsk+Fmod+ subset of PCs in jaw bones. The Ctsk+Fmod+ PCs had the potential of multi-directional differentiation. Furthermore, Spp1 secreted by macrophages could impair the osteogenic capacity of Ctsk+Fmod+ PCs, which could be partly rescued by blocking Spp1. The identification of this Ctsk+Fmod+ subclusters, which shows osteoprogenitor characteristics and close interaction with macrophages, reveals the heterogeneity of periosteal cells in jaw bones, and may provide target of intervention to improve osteogenesis during bone augmentation surgery.