Multi-omic analysis of jaw-bone periosteum identifies the role of macrophage-derived SPP1 in Ctsk+Fmod+ periosteal cells

Abstract Periosteal cells (PCs) play a crucial role in bone regeneration. Currently, the spatial landscapes of jaw-bone periosteum during bone grafting remains unclear. In this study, we propose a modified guided bone regeneration (GBR) model and integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to dissect its spatial characteristics. We identify a functional subset of Ctsk + Fmod + PCs within the jaw-bone periosteum of rat and human. In addition, we describe a spatial niche around the bone graft substitute, characterized by massive infiltration of macrophages interacting with Ctsk + Fmod + PCs. Notably, SPP1 secreted by macrophages attenuates the osteogenic capacity of Ctsk + Fmod + PCs. The discovery of this Ctsk + Fmod + subcluster, characterized by osteoprogenitor features and close interactions with macrophages, sheds light on the composition of the subperiosteal microenvironment and the heterogeneity of jaw-bone PCs.