期刊
THERANOSTICS
卷 10, 期 1, 页码 17-35出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.36930
关键词
Macrophage scavenger receptor 1; Bone marrow stem cells; Osteogenic differentiation; Oxidative phosphorylation; PI3K/AKT/GSK3 beta/beta-catenin pathway
资金
- National Natural Science Foundation of China [81772351, 81520108018, 81472080, 81772352, 81401800]
- Jiangsu Committee of Science and Technology-Social Development Plan [BE2017755]
- Jiangsu Six Talents Peak [WSN-011]
- Nanjing Committee of Science and Technology [201505005]
- Medical Science and technology development Foundation from Nanjing Department of Health [YKK17060]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX18_0430]
Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socioeconomic implications. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiation through the osteogenic pathway during fracture healing has attracted much attention. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossification (IO) in vivo. The potential functions and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed IO in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3 beta/beta-catenin signaling increased ability to promote osteogenic differentiation of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3 beta/beta-catenin pathway in the co-culture system that facilitated M2-like polarization by enhancing mitochondrial oxidative phosphorylation. Conclusion: Our findings revealed a previously unrecognized function of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.
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