1 Department of Endodontology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
2 Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
J Dent Res. 2018 Jul;97(8):859-868. doi: 10.1177/0022034518764411. Epub 2018 Mar 22.
Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes, microvesicles, and apoptotic bodies. EVs are released by most cell types, such as bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone-remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor β1) to osteoblasts and regulate bone formation. In addition, EVs can deliver cytokines, such as RANK (receptor activator of nuclear factor κB) and RANKL (RANK ligand), and microRNAs, such as miR-218 and miR-148a, to modulate osteoclast differentiation during bone resorption. EVs also transfer bioactive molecules and have targeted therapies in bone-related diseases. Moreover, bioactive molecules in EVs are biomarkers in bone-related diseases. We highlight the emerging role of EVs in bone remodeling during physiologic and pathologic conditions and summarize the role of EVs in tooth development and regeneration. At the end of this review, we discuss the challenges of EV application in the treatment of bone diseases.
细胞外囊泡(EVs)作为纳米级颗粒,包括外泌体、微囊泡和凋亡小体。EVs 由大多数细胞类型释放,如骨髓干细胞、成骨细胞、破骨细胞和免疫细胞。在骨重塑微环境中,EVs 向成骨细胞传递特定的蛋白质(如 tenascin C 和 Sema4D)、microRNAs(如 miR-214-3p、miR-183-5p 和 miR-196a)和其他生长因子(如骨形态发生蛋白 1 至 7 和转化生长因子 β1),调节骨形成。此外,EVs 可以传递细胞因子,如 RANK(核因子 κB 受体激活物)和 RANKL(RANK 配体),以及 microRNAs,如 miR-218 和 miR-148a,来调节破骨细胞在骨吸收过程中的分化。EVs 还可以传递生物活性分子,并在骨相关疾病中具有靶向治疗作用。此外,EV 中的生物活性分子是骨相关疾病的生物标志物。我们强调了 EV 在生理和病理条件下骨重塑中的新兴作用,并总结了 EV 在牙齿发育和再生中的作用。在这篇综述的最后,我们讨论了 EV 在骨疾病治疗中的应用所面临的挑战。