Ma Qinyu, Liang Mengmeng, Wu Yutong, Luo Fei, Ma Zaisong, Dong Shiwu, Xu Jianzhong, Dou Ce
Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Department of Biomedical Materials Science, Third Military Medical University, Chongqing, 400038, China.
Bone Res. 2021 Jan 11;9(1):5. doi: 10.1038/s41413-020-00121-1.
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 CD31Emcn 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.
骨重塑由骨吸收和形成精确协调。凋亡的破骨细胞产生大量凋亡小体（ABs），标志着骨吸收阶段的结束，而破骨细胞衍生的ABs的功能在很大程度上仍不清楚。在这里，我们确定了来自不同分化阶段破骨细胞的ABs的分子特征，并研究了它们相应的功能。ABs从由星形孢菌素诱导凋亡的骨髓巨噬细胞、前破骨细胞和成熟破骨细胞中分离出来。液相色谱-串联质谱的蛋白质组学特征分析表明，不同的ABs之间存在明显的蛋白质货物差异。进一步的生物信息学分析表明，ABs的蛋白质组学特征与其亲代细胞的高度相似。在功能上，在小鼠骨缺损模型中，前破骨细胞来源的ABs（pOC-ABs）通过其血小板衍生生长因子-BB（PDGF-BB）货物诱导内皮祖细胞分化并增加CD31Emcn内皮细胞形成。成熟破骨细胞来源的ABs（mOC-ABs）通过RANKL反向信号诱导间充质干细胞的成骨分化并促进骨生成。总之，我们描绘了破骨细胞衍生的ABs的详细蛋白质组学图谱，并表明它们在骨重塑过程中将骨形成与吸收耦合方面的潜在生物学作用很重要。
