Mgp High‐Expressing MSCs Orchestrate the Osteoimmune Microenvironment of Collagen/Nanohydroxyapatite‐Mediated Bone Regeneration

Author:

Wan Zhuqing12,Bai Xiaoqiang12,Wang Xin12,Guo Xiaodong12,Wang Xu12,Zhai Mo12,Fu Yang12,Liu Yunsong12,Zhang Ping12,Zhang Xiao12,Yang Ruili23,Liu Yan23,Lv Longwei12,Zhou Yongsheng12ORCID

Affiliation:

1. Department of Prosthodontics Peking University School and Hospital of Stomatology Haidian District Beijing 100081 China

2. National Center for Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology, Key Laboratory of Digital Stomatology Chinese Academy of Medical Sciences Haidian District Beijing 100081 China

3. Department of Orthodontics Peking University School and Hospital of Stomatology Haidian District Beijing 100081 China

Abstract

AbstractActivating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial‐mediated bone regeneration, a comprehensive single‐cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite‐based bone repair materials via combining analysis of single‐cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high‐expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand–receptor pair. The inhibition of Mdk/Lrp1 activates the pro‐inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune‐cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial‐mediated bone regeneration and provide the basis for materials‐designed strategies that target osteoimmune modulation.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Beijing Municipality

China Postdoctoral Science Foundation

Publisher

Wiley

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