已知，牙周炎致牙槽骨代谢破坏过程中存在骨吸收和重建间稳态失调现象，且破骨细胞骨吸收过程中旁分泌产物具有调控骨形成/成骨细胞分化作用，但具体生物通讯物质及机制至今未明。新近,我们率先发现破骨细胞来源外泌体（mOC-exo）可调控成骨细胞JAK2/STAT3信号传导抑制成骨细胞分化；且mOC-exo递送miR-135可穿梭进入成骨样细胞，但调控机制不详。本项目在此研究基础上拟应用CRISPR/Cas9技术、双荧光素酶报告基因检测等手段探究mOC-exo影响成骨细胞分化而扰乱牙槽骨吸收与形成间失衡的生物学功能；鉴定mOC-exo递送miR-135与成骨细胞JAK2可能存在的结合位点，重点关注miR-135沉默RUNX2转录活性，调控RANKL、OPG级联反应的分子机制，诠释mOC-exo在牙槽骨代谢稳态破坏过程中所扮演角色，有望为牙周病治疗提供可能的干预靶点，具有重要科学理论意义和潜在应用价值。

It is known that periodontitis is associated with imbalance between bone resorption and remodeling during the process of alveolar bone metabolism destruction. Paracrine products derived from osteoclast bone resorption can regulate bone formation and osteoblast differentiation. However, the mechanism of specific bio-communication substances is still unknown. Our preliminary study first found that the exosome derived from osteoclast resorption (mOC-exo) is a pivotal communicational substance, and it could significantly regulate the JAK2/STAT3 signaling pathway of osteoblasts as well as osteoblast differentiation. We further discovered that miR-135 delivered by the exosome mOC-exo could shuttle into osteoblasts, whereas its specific communicational mechanism is unknown. Based on the above findings, this project will investigate the biological functions of mOC-exo that affects osteoblasts differentiation and consequently disrupts the absorption and formation of alveolar bone using CRISPR/Cas9 technology, dual luciferase reporter gene detection etc. Moreover，we will testify the site of interaction between miR-135 and the target gene JAK2, and focus on the molecular mechanism of miR-135 inhibiting transcriptional activity of RUNX2 and regulating RANKL and OPG cascades. The expected data may elucidate the role of mOC-exo in the process of the destruction of alveolar bone metabolism, and it may provide a potential intervention target for periodontal disease treatment, which has important scientific theoretical significance and potential application value.