Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Beijing, 100081, China.
National Center of Stomatology, National Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Small. 2023 Apr;19(16):e2205813. doi: 10.1002/smll.202205813. Epub 2023 Jan 20.
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.
间充质干细胞（MSCs）被广泛应用于疾病治疗。在体内应用后，MSCs 会发生凋亡并释放凋亡小体（apoVs）。本研究旨在探讨来源于人骨髓间充质干细胞（hBMMSCs）的 apoVs 在骨代谢中的作用及其作用机制。研究结果表明，apoVs 可以在体外和体内促进成骨和抑制破骨细胞形成。因此，apoVs 可能减轻原发性和继发性骨质疏松症引起的骨丢失，并刺激骨缺损区域的骨再生。apoV 诱导骨再生的机制包括释放 miR1324，其抑制靶基因分选连接蛋白 14（SNX14）的表达，从而激活靶细胞中的 SMAD1/5 通路。鉴于 MSC 衍生的 apoVs 易于获得和储存，且免疫排斥和肿瘤转化的风险较低，因此，该研究为治疗骨丢失提供了一种新的治疗策略，包括通过无细胞的方法进行骨组织工程。
