Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory for Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, 100081, P. R. China.
Adv Sci (Weinh). 2024 Sep;11(36):e2402529. doi: 10.1002/advs.202402529. Epub 2024 Aug 5.
Treatment strategies for hard tissue defects aim to establish a mineralized microenvironment that facilitates tissue remodeling. As a mineralized tissue, cementum shares a similar structure with bone and exhibits an excellent capacity to resist resorption under compression. Macrophages are crucial for mineralized remodeling; however, their functional alterations in the microenvironment of cementum remain poorly understood. Therefore, this study explores the mechanisms by which cementum resists resorption under compression and the regulatory roles of cementoblasts in macrophage functions. As a result, extracellular vesicles from compression-loaded cementoblasts (Comp-EVs) promote macrophage M2 polarization and enhance the clearance of apoptotic cells (efferocytosis) by 2- to 3-fold. Local injection of Comp-EVs relieves cementum destruction in mouse root resorption model by activating the tissue repair function of macrophages. Moreover, Comp-EV-loaded hydrogels achieve significant bone healing in calvarial bone defect. Unexpectedly, under compression, EV secretion in cementoblasts is reduced by half. RNA-Seq analysis and verification reveal that Rab35 expression decreases by 60% under compression, thereby hampering the release of EVs. Rab35 overexpression is proposed as a modification of cementoblasts to boost the yield of Comp-EVs. Collectively, Comp-EVs activate the repair function of macrophages, which will be a potential therapeutic strategy for hard tissue repair and regeneration.
硬组织缺损的治疗策略旨在建立一个有利于组织重塑的矿化微环境。作为一种矿化组织，牙骨质与骨具有相似的结构，并具有在压缩下抵抗吸收的优异能力。巨噬细胞对于矿化重塑至关重要；然而，它们在牙骨质微环境中的功能变化仍知之甚少。因此，本研究探讨了牙骨质在压缩下抵抗吸收的机制以及成牙骨质细胞在巨噬细胞功能中的调节作用。结果表明，来自受压牙骨质细胞的细胞外囊泡（Comp-EVs）可促进巨噬细胞 M2 极化，并将细胞凋亡（噬作用）的清除率提高 2-3 倍。通过激活巨噬细胞的组织修复功能，局部注射 Comp-EVs 可减轻小鼠牙根吸收模型中的牙骨质破坏。此外，Comp-EV 负载水凝胶可在颅骨骨缺损中实现显著的骨愈合。出乎意料的是，在受压下，牙骨质细胞中的 EV 分泌减少了一半。RNA-Seq 分析和验证表明，Rab35 的表达在受压下降低了 60%，从而阻碍了 EV 的释放。提出 Rab35 过表达作为牙骨质细胞的修饰，以提高 Comp-EVs 的产量。总之，Comp-EVs 激活了巨噬细胞的修复功能，这将是硬组织修复和再生的一种潜在治疗策略。
