Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling.

Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling.
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破骨细胞衍生的凋亡小体在骨重塑中耦合骨吸收和形成

DOI:
10.1038/s41413-020-00121-1
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发表时间:
2021-01-11
期刊:
影响因子:
12.7
通讯作者:
Dou C
Dou C
中科院分区:
医学1区
文献类型:
--
作者:
Ma Q;Liang M;Wu Y;Luo F;Ma Z;Dong S;Xu J;Dou C

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骨重建与骨吸收和骨形成密切相关。凋亡的破骨细胞产生大量的凋亡小体(ABS),标志着骨吸收阶段的结束,而破骨细胞来源的ABS的功能在很大程度上仍不清楚。在这里,我们鉴定了不同分化阶段的破骨细胞来源的ABS的分子图谱,并研究了它们相应的功能。从星状孢子素诱导的凋亡的骨髓巨噬细胞、破骨前细胞和成熟破骨细胞中分离出ABS。用液相色谱-串联质谱仪进行蛋白质组特征分析表明,不同ABS之间的蛋白质组分存在显著差异。进一步的生物信息学分析表明,ABS的蛋白质组特征与其亲本细胞的蛋白质组特征高度相似。在功能上,POC-ABS通过其PDGF-BB载体诱导内皮祖细胞分化并增加CD31hiEmcnhi内皮细胞的形成。MOC-ABS通过RANKL反向信号通路诱导间充质干细胞向成骨细胞分化,促进成骨。综上所述,我们绘制了破骨细胞来源的ABS的详细蛋白质组图谱,并表明它们在骨重建过程中结合骨形成和骨吸收的潜在生物学作用是重要的。
Bone remodeling is precisely coordinated by bone resorption and formation. Apoptotic osteoclasts generate large amounts of apoptotic bodies (ABs) marking the end of the bone resorption phase, whereas the functions of osteoclast-derived ABs remain largely unknown. Here, we identified the molecular profile of ABs derived from osteoclasts at distinct differentiation stages and investigated their corresponding functions. ABs were isolated from apoptotic bone marrow macrophages, preosteoclasts, and mature osteoclasts induced by staurosporine. Proteomic signature analysis with liquid chromatography-tandem mass spectrometry suggested marked protein cargo differences among the different ABs. Further bioinformatic analysis showed that the proteomic signatures of the ABs were highly similar to those of their parental cells. Functionally, pOC-ABs induced endothelial progenitor cell differentiation and increased CD31hiEmcnhi endothelial cell formation in a murine bone defect model via their PDGF-BB cargo. mOC-ABs induced osteogenic differentiation of mesenchymal stem cells and facilitated osteogenesis via RANKL reverse signaling. In summary, we mapped the detailed proteomic landscapes of ABs derived from osteoclasts and showed that their potential biological roles are important in coupling bone formation with resorption during bone remodeling.
破骨细胞来源的外泌体 miR-214-3p 抑制成骨细胞骨形成
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影响因子: 16.6
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