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.

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Funding

the National Natural Science Foundation of China, grant 82271015

the National Natural Science Foundation of China, grant 82201106； Research Funding from West China School/Hospital of Stomatology, Sichuan University (No. RCDWJS2023-8).

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