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

Abstract

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.

The GgcxK325Q Mutation Does Not Affect the Calcium Homeostasis of the Epididymis and Male Fertility in Mice

“…We speculate that the different expression patterns in the mouse and rat epididymis are caused by species differences. A large number of studies have demonstrated that MGP plays an indispensable role in calcium regulation, especially in organs or tissues where it is highly expressed, such as bone and blood vessels [ 9 , 31 , 32 , 33 ]. Similarly, MGP was highly expressed in the initial segment of the mouse epididymis and colocalized with GGCX in this region.…”

Dynamic Cross-Linking, Self-Healing, Antibacterial Hydrogel for Regenerating Irregular Cranial Bone Defects

“…Moreover, critical-sized bone defects are those where spontaneous osseointegration cannot occur without additional surgical intervention . While autologous bone grafts are vital for cranial bone defect reconstruction, they are constrained by autologous bone resorption and muscle tissue growth within the bone gap. , Alternative solutions such as allografts, peptide meshes, PEEK, and others address sourcing issues but are limited by immune rejection and infection transmission risks. To overcome these challenges, biomaterials in bone tissue engineering are gaining increasing attention. , Various materials such as metals, alloys, bioceramics, and polymers have been developed as alternative bone grafts.…”