假体周围骨溶解所致的人工关节无菌性松动尚缺乏有效防治手段。近年研究证明：SOST 基因及其蛋白sclerostin是骨细胞参与骨重建，调控成骨和破骨细胞的关键分子。预试验发现骨细胞、SOST/sclerostin 与假体周围骨溶解存在一定联系，但其机制不明确。在既往骨溶解机制研究基础上。拟通过：1）已构建的鼠骨溶解模型，检测SOST的表达，经sclerostin 抗体阻断，观察假体周围骨整合的变化。2）在磨损颗粒条件下，观察离体培养骨细胞功能的变化和SOST的表达，靶向干扰SOST后，再次观察其变化。并将SOST 干扰前后的骨细胞分别与成骨和破骨细胞共培养，观察其对成骨和破骨特征性标记物和OPG/RANKL信号通路的影响。以此探索骨细胞通过SOST/sclerostin调节成骨细胞和破骨细胞功能，参与假体周围骨溶解的机制，为开辟关节无菌性松动的靶向治疗提供理论依据。

Periprosthetic osteolysis mediated by wear debris is the principal cause of aseptic loosening which is the main complication of joint arthroplasty. However, there is still no effective way to prevention and treatment of prosthetic loosening. Recently, some studies showed that SOST gene and sclerostin, the protein product of SOST， were associated with sclerosteosis, fracture healing and osteoporosis. SOST/sclerostin inhibited bone formation and increased bone resorption through depression of osteoblast activity and promotion of osteoclast activity. Osteocyte which express SOST and sclerostin exclusively in the adult skeleton played an important role of regulation bone remodeling. Our latest research found osteocyte, SOST and sclerostin were concerned with periprosthetic osteolysis. But the mechanism has not been clearly clarified. Based on our previous study of osteolysis mechanism and the latest reports, we have a hypothesis that SOST gene and sclerostin play an important role in the effect of osteocyte on periprosthetic osteolysis. To test the hypothesis, we will plan to build the osteolysis model of SD rats and detect the expression of SOST and sclerostin. Then treating rats with sclerostin antibody, new bone formation and periprosthetic osteointergration will be assessed by using histomorphology, Micro-CT, mechanical pull-out test, and so on. Osteocytes will be cultivated with different concentration of particulates titanium alloy. cell proliferation, apoptosis, gene and protein expression of OPG/RANKL, SOST and sclerostin , the characteristic marker and inflammatory cytokine such as IL-1, TNF, MMP-2 will be evaluated or measured by Brdu assey, flow cytometry, real-time PCR, Western Blot and Elisa kit respectively. After downregulation SOST expression by RNA interference, the change of osteocyte will be detected again. Furthermore, osteocyte with siRNA-SOST gene will be co-cultured with osteoblast and osteoclast respectively. Then the characteristic marker will be detected to evaluate the anabolic state of osteoblast and the catabolic state of osteoclast. The effect of SOST and sclerostin on OPG/RANKL signaling pathways also will be examined. Through a series of experiments, we want to confirm our hypothesis and explict the role of SOST and sclerostin on osteocyte regulating osteoblast and osteoclast in the process of periprosthetic osteolysis. Therefore the research may provide a scientific basis for SOST/sclerostin as a target for prevention and cure of periprosthetic osteolysis and joint loosening.