Molecular Profiling of Osteoclast Derived Apoptotic Bodies Reveals Extended Intercellular Regulations after Cell Death

Increasing evidences are revealing the important biological functions of apoptotic bodies (ABs). Here we identified the proteomic profiles of ABs from osteoclasts of distinct differentiation stages and investigated the potential functions. ABs were isolated from apoptotic bone marrow macrophages (BMMs), pre-osteoclasts (pOCs) or mature osteoclasts (mOCs). Proteomic signature analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by bioinformatic analysis showed that proteomic signatures of ABs exhibited high similarities with the parental cells. Functionally, pOC-ABs induced endothelial progenitor cell (EPC) differentiation and increased CD31hiEmcnhi endothelial cell formation in a murine bone defect model via PDGF-BB. mOC-ABs induced mesenchymal stem cell (MSC) osteogenic differentiation and promoted bone formation via RANKL reverse signaling. Together, our results mapped the detailed proteomic landscapes of osteoclast derived ABs and demonstrated that the biological functions of ABs are largely inherited from corresponding parental cells, suggesting a novel extended intercellular regulation after cell apoptosis.