Osteoclast-derived small extracellular vesicles induce osteogenic differentiation via inhibiting ARHGAP1
| Autor: | Qinyu Ma, Fei Luo, Ce Dou, Jianzhong Xu, Hongbo Ai, Shuai Zhang, Shiwu Dong, Xiaofan Yin, Mengmeng Liang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Macrophage colony-stimulating factor musculoskeletal diseases viruses osteogenic differentiation Bone remodeling 03 medical and health sciences 0302 clinical medicine Osteoclast Drug Discovery medicine Bone regeneration biology Chemistry Regeneration (biology) Mesenchymal stem cell lcsh:RM1-950 virus diseases respiratory system Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology RANKL 030220 oncology & carcinogenesis osteoclast biology.protein Molecular Medicine Original Article Bone marrow extracellular vesicles |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 23, Iss, Pp 1191-1203 (2021) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | Activated osteoclasts release large amounts of small extracellular vesicles (sEVs) during bone remodeling. However, little is known about whether osteoclast-derived sEVs affect surrounding cells. In this study, osteoclasts were generated by stimulating bone marrow macrophages (BMMs) with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear actor κB ligand (RANKL). We performed microarray analysis of sEV-microRNAs (miRNAs)s secreted from osteoclast at different stages and identified four miRNAs that were highly expressed in mature osteoclast-derived sEVs. One of these miRNAs, miR-324, significantly induced osteogenic differentiation and mineralization of primary mesenchymal stem cells (MSCs) in vitro by targeting ARHGAP1, a negative regulator of osteogenic differentiation. We next fabricated an sEV-modified scaffold by coating decalcified bone matrix (DBM) with osteoclast-derived sEVs, and the pro-osteogenic regeneration activities of the sEV-modified scaffold were validated in a mouse calvarial defect model. Notably, miR-324-enriched sEV-modified scaffold showed the highest capacity on bone regeneration, whereas inhibition of miR-324 in sEVs abrogated these effects. Taken together, our findings suggest that miR-324-contained sEVs released from mature osteoclast play an essential role in the regulation of osteogenic differentiation and potentially bridge the coupling between osteoclasts and MSCs. Graphical Abstract Liang et al. describe a novel mode of communication between osteoclasts and mesenchymal stem cells during bone remodeling. Specifically, miR-324-enriched sEVs derived from osteoclasts promote osteogenic differentiation via ARHGAP1/RhoA/ROCK signaling. |
| Databáze: | OpenAIRE |
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