Apoptotic Vesicles Regulate Bone Metabolism via the miR1324/SNX14/SMAD1/5 Signaling Axis

Abstract Mesenchymal stem cells (MSCs) are widely used in the treatment of diseases. After their in vivo application, MSCs undergo apoptosis and release apoptotic vesicles (apoVs). This study investigates the role of apoVs derived from human bone marrow mesenchymal stem cells (hBMMSCs) in bone metabolism and the molecular mechanism of the observed effects. The results show that apoVs can promote osteogenesis and inhibit osteoclast formation in vitro and in vivo. ApoVs may therefore attenuate the bone loss caused by primary and secondary osteoporosis and stimulate bone regeneration in areas of bone defect. The mechanisms responsible for apoV‐induced bone regeneration include the release of miR1324, which inhibit expression of the target gene Sorting Nexin 14 (SNX14) and thus activate the SMAD1/5 pathway in target cells. Given that MSC‐derived apoVs are easily obtained and stored, with low risks of immunological rejection and neoplastic transformation, The findings suggest a novel therapeutic strategy to treat bone loss, including via cell‐free approaches to bone tissue engineering.