State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
Qingdao Stomatological Hospital Affiliated to Qingdao University, No.17 Dexian Road, Shinan District, Qingdao, 266001, Shandong Province, China.
J Nanobiotechnology. 2024 Oct 26;22(1):658. doi: 10.1186/s12951-024-02934-2.
BACKGROUND: Apoptotic vesicles (ApoVs), which are extracellular vesicles released by apoptotic cells, have been reported to exhibit substantial therapeutic potential for inflammatory diseases and tissue regeneration. While extensive research has been dedicated to mesenchymal stem cells (MSCs), the investigation into immune cell-derived ApoVs remains limited, particularly regarding the function and fate of macrophage-derived ApoVs in the context of periodontitis (PD).
Our study corroborates the occurrence and contribution of resident macrophage apoptosis in Porphyromonas gingivalis (Pg)-associated PD. The findings unveil the pivotal role played by apoptotic macrophages and their derived ApoVs in orchestrating periodontal bone remodeling. The enrichments of diverse functional miRNAs within these ApoVs are discerned through sequencing techniques. Moreover, our study elucidates that the macrophage-derived ApoVs predominantly deliver miR-143-3p, targeting insulin-like growth factor-binding protein 5 (IGFBP5), thereby disrupting periodontal bone homeostasis.
Our study reveals that macrophages in Pg-associated PD undergo apoptosis and generate miR-143-3p-enriched ApoVs to silence IGFBP5, resulting in the perturbation of osteogenic-osteoclastic balance and the ensuing periodontal bone destruction. Accordingly, interventions targeting miR-143-3p in macrophages or employment of apoptosis inhibitor Z-VAD hold promise as effective therapeutic strategies for the management of PD.
背景：凋亡小体（ApoV）是由凋亡细胞释放的细胞外囊泡，已被报道在炎症性疾病和组织再生方面具有很大的治疗潜力。虽然已经对间充质干细胞（MSCs）进行了广泛的研究，但对免疫细胞来源的 ApoV 的研究仍然有限，特别是关于巨噬细胞来源的 ApoV 在牙周炎（PD）背景下的功能和命运。
我们的研究证实了牙周致病菌牙龈卟啉单胞菌（Pg）相关 PD 中常驻巨噬细胞凋亡的发生和贡献。研究结果揭示了凋亡巨噬细胞及其衍生的 ApoV 在协调牙周骨重塑中的关键作用。通过测序技术可以识别这些 ApoV 中不同功能 miRNA 的富集。此外，我们的研究表明，巨噬细胞来源的 ApoV 主要传递 miR-143-3p，靶向胰岛素样生长因子结合蛋白 5（IGFBP5），从而破坏牙周骨稳态。
我们的研究表明，Pg 相关 PD 中的巨噬细胞发生凋亡并产生富含 miR-143-3p 的 ApoV，沉默 IGFBP5，导致成骨-破骨平衡失调和随后的牙周骨破坏。因此，针对巨噬细胞中的 miR-143-3p 或使用凋亡抑制剂 Z-VAD 的干预措施有望成为 PD 管理的有效治疗策略。
