Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

牙周炎是由破骨细胞活性过度活跃引起的，导致牙周支持组织丧失，而间充质干细胞（MSC）对于牙周再生至关重要。然而，牙周炎期间缺氧的牙周微环境会诱导MSCs凋亡。凋亡小体（ABs）是凋亡细胞的主要产物，作为牙周炎治疗的潜在介质而受到越来越多的关注，因此我们研究了源自MSCs的ABs对牙周炎的影响。MSCs来源于小鼠骨髓，在低氧条件下培养72小时，然后使用多重过滤系统从培养上清液中分离ABs。结果表明，源自 MSC 的 AB 抑制破骨细胞分化和牙槽骨吸收。miRNA 阵列分析表明，miR-223-3p 在这些 AB 中高度富集，对其治疗效果至关重要。Targetscan和荧光素酶活性结果证实Itgb1是miR-223-3p的靶标，它干扰破骨细胞的功能。此外，DC-STAMP 是介导膜输注的关键调节剂。AB 和前破骨细胞在其膜上表达高水平的 DC-STAMP，介导前破骨细胞吞噬 AB。DC-STAMP 敲低的 AB 未能被前破骨细胞吞噬。总的来说，MSC 衍生的 AB通过DC-STAMP被前破骨细胞吞噬，通过将 miR-223-3p 转移到破骨细胞来挽救牙槽骨丢失，进而导致其分化和骨吸收减弱。这些结果表明 MSC 衍生的 AB 是治疗牙周炎的有前途的治疗剂。