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 CD31^hiEmcn^hi 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.

骨重塑通过骨吸收和形成来精确协调。凋亡的破骨细胞产生大量的凋亡小体（AB），标志着骨吸收阶段的结束，而破骨细胞衍生的AB的功能仍然未知。在这里，我们确定了从破骨细胞衍生的ABs在不同分化阶段的分子特征，并研究了它们的相应功能。从凋亡的骨髓巨噬细胞，破骨细胞和星形孢菌素诱导的成熟破骨细胞中分离出AB。用液相色谱-串联质谱进行蛋白质组学特征分析表明，不同AB之间存在明显的蛋白质负载差异。进一步的生物信息学分析表明，AB的蛋白质组学特征与其亲代细胞高度相似。在功能上^喜Emcn^喜内皮细胞的形成中通过它们的PDGF-BB的货物的鼠骨缺损模型。mOC-ABs诱导间充质干细胞的成骨分化，并通过RANKL反向信号促进成骨。总之，我们绘制了由破骨细胞衍生的AB的详细蛋白质组学图谱，并显示了其潜在的生物学作用在骨重塑过程中对骨形成与吸收的耦合至关重要。