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

• Published in: Advanced science Vol. 11; no. 23; pp. e2308986 - n/a
• Main Authors: Wan, Zhuqing, Bai, Xiaoqiang, Wang, Xin, Guo, Xiaodong, Wang, Xu, Zhai, Mo, Fu, Yang, Liu, Yunsong, Zhang, Ping, Zhang, Xiao, Yang, Ruili, Liu, Yan, Lv, Longwei, Zhou, Yongsheng
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.06.2024; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Biocompatible Materials; biomaterials; Biomedical materials; Bone density; Bone Regeneration - genetics; Bone Regeneration - immunology; Bones; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cell Differentiation - genetics; Collagen; Collagen - genetics; Collagen - metabolism; Defects; Durapatite - metabolism; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Gene expression; Homeostasis; Hydrogels; Matrix Gla Protein; mesenchymal stem cells; Mesenchymal Stem Cells - immunology; Mesenchymal Stem Cells - metabolism; Mice; Neutrophils; Osteogenesis - drug effects; Osteogenesis - genetics; Osteogenesis - immunology; osteoimmune microenvironment; Quantitative analysis; single‐cell transcriptomics; spatial transcriptomics; Stem cells; Tissue engineering; osteoimmune microenvironment; biomaterials; single‐cell transcriptomics; mesenchymal stem cells; spatial transcriptomics
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202308986

Activating 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. This study reveals how collagen/nanohydroxyapatite‐based bone repair materials regulate the osteoimmune microenvironment via combining single‐cell RNA sequencing and spatial transcriptomics analyses. The Mgp high‐expressing MSCs with efficient osteogenic differentiation potential are found to be aggregated around implanted materials at the early stage of bone regeneration, regulating the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand–receptor pair.