正畸诱导性炎性牙根吸收是正畸力作用下成牙骨质细胞和破骨细胞协调作用失衡致使牙骨质等牙体组织破坏的并发症。研究表明，在PTH的作用下高表达的成骨细胞外泌体RANKL可通过识别破骨细胞膜受体RANK上调转录因子NFATc1的表达促进破骨细胞分化激活。进一步的研究指出，在骨折的老年女性中破骨细胞外泌体miR-214-3p表达升高进而下调成骨细胞转录因子ATF-4抑制成骨细胞活性。然而，关于成牙骨质细胞外泌体在牙骨质代谢中的作用尚知之甚少。因此，本项目组根据前期基础拟着重研究：①炎症诱导的成牙骨质细胞外泌体对破骨细胞功能活性的影响；②成牙骨质细胞外泌体miRNA基于RANK/TRAF6/c-Fos与OPG/RANKL/RANK信号轴调控破骨细胞功能的分子机制；③正畸牙移动动物模型中成牙骨质细胞外泌体与牙根吸收的关联；以探讨成牙骨质细胞外泌体调控破骨细胞功能活性参与正畸牙骨质代谢的生物机制。

Orthodontically induced inflammatory root resorption (OIIRR) is a common complication with the destruction of cementum and other dental tissues due to the imbalance of cementoblasts and osteoclasts upon orthodontic force. Recent studies reported that the expression of RANKL in osteoblast-derived exosomes is elevated upon PTH stimulation, which up-regulated the expression of NFATc1 via recognizing the osteoclasts surface receptor RANK and promoted osteoclasts activation. Further study showed that in elderly bone-fracture women, the increased osteoclast-derived exosomes miR-214-3p inhibited osteoblasts activity by decreasing the transcription factor ATF-4. However, the effects of cementoblast-derived exosomes in the metabolism of cementum are largely unknown. According to our pilot study, the following scientific studies are proposed to explore the biological mechanism of cementoblast-derived exosomes involved in cementum metabolism by regulating osteoclasts functional activity: (1) The effects of inflammatory factors-induced cementoblast-derived exosomes on osteoclasts function; (2) The effects of cementoblast-derived exosomes on regulation of osteoclasts based on the RANK/TRAF6/c-Fos and OPG/RANKL/RANK signal pathways; (3) The correlation between functional molecules within cementoblast-derived exosomes and orthodontically induced inflammatory root resorption in the animal model of OIIRR.