人工假体磨损颗粒作用下 Wnt/β-catenin 信号通路对成骨细胞的影响.

Effect of Wnt/beta-catenin signaling pathway on osteoblasts under the action of wear particles.

BACKGROUND: With the progress of the mid-term and long-term follow-up study, it is found that the periprosthesis loosening is an important factor that limits the service life of artificial prosthesis and restricts the development of artificial joint replacement. OBJECTIVE: To further understand the Wnt/β-catenin signaling pathway and provide new targets for drug therapy by analyzing the research results of main signal factors of Wnt/β-catenin signaling pathway on osteoblasts and the cell function of osteoblast origin. METHODS: The first author searched the literature published from 2005 to 2020 by computer with the Chinese key words of “wear debris, peri-prosthetic osteolysis, aseptic loosening, pathogenesis, osteoblast, signaling pathway, bone remodeling, Wnt/β-catenin” in the databases of CNKI, Wanfang and VIP, and with the English key words of “wear debris, wear particles, peri-prosthetic osteolysis, PPO, aseptic loosening, AL, pathogenesis, osteoblast, OB, signal path, bone remodeling, Wnt/β-catenin” in PubMed and Web of Science. The articles regarding the effect and mechanism of Wnt/β-catenin pathway on osteoblasts under the influence of wear particles were collected. Finally, 53 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: (1) During the pathological process of wear particle induced osteolysis around implant and aseptic loosening, Wnt/β-catenin signaling pathways activated by inhibiting bone-forming formation and increasing bone resorption, in turn, affects bone reconstruction, and has played a key role in the pathology of wear particle induced osteolysis around implant and aseptic loosening. (2) In vitro experiments, Wnt/β-catenin signaling pathways were activated by GSK-3β inhibitor LiCl, growth hormone release polypeptide, and protein phosphatase 2A inhibition to promote osteoblast differentiation and osteogenic activity. However, ICG-001 inhibitor blocked the β-catenin signaling pathway, thus weakening the protective effect of LiCl on osteoblastic differentiation, suggesting that GSK-3/β-catenin signaling pathway may be an important mechanism mediating Ti wear particles to induce osteolysis around the prosthesis. (3) In vivo experiments, the application of SOST antibody, protein phosphatase 2A inhibition, LiCl, AR28 and other ways through activation of Wnt/β-catenin and other signal pathways can promote bone formation, inhibit osteoclast absorption, increase local bone mass and bone volume, and resist the effect of osteolysis around the prosthesis induced by Ti and other wear particles. (4) At the gene level, the activity and mineralization of MC3T3-E1 cells were also significantly enhanced under SOST silencing condition, even when treated with titanium particles. On the contrary, the decreased expression level of SOST increased the expression level of β-catenin. The results suggested that the decrease of SOST gene expression could activate the Wnt/β-catenin signaling pathway to promote bone formation and improve the bone loss caused by Ti particles. [ABSTRACT FROM AUTHOR]

背景：随着人工关节置换后中远期随访研究的推进发现，置换后中远期出现假体周围松动是限制人工假体使用年限、制约人工关节置换 发展的重要因素。 目的：通过梳理磨损颗粒诱导下Wnt/β-catenin信号通路主要信号因子对成骨细胞及成骨细胞来源细胞功能方面的研究成果，以进一步深入 理解Wnt/β-catenin信号通路，并为药物治疗等提供新的靶点。 方法：由第一作者应用计算机检索 2005至2020年出版的文献，中文以“磨损颗粒，假体周围骨溶解，假体无菌性松动，发病机制，成骨细 胞，信号通路，骨重建，Wnt/β-catenin”检索知网、万方、维普数据库；英文以“wear debris，wear particles，peri-prosthetic osteolysis， PPO，Aseptic loosening，AL，Pathogenesis，osteoblast，OB，Signal path，bone remodeling，Wnt/β-catenin”检索 PubMed和Web of Science 数据库，收录与磨损颗粒影响下Wnt/β-catenin通路主要对成骨细胞的影响及作用机制相关的文献报道，按照入选标准共纳入53篇文章。 结果与结论：①磨损颗粒诱导假体周围骨溶解、无菌性松动的病理过程中，Wnt/β-catenin信号通路激活后通过抑制成骨形成、增加破骨吸 收进而影响骨重建，在磨损颗粒诱导假体周围骨溶解、无菌性松动的病理过程中起到了关键性的作用；②在体外实验中，通过应用GSK-3β 抑制剂LiCl、生长激素释放多肽以及蛋白磷酸酶2A抑制可以激活Wnt/β-catenin等信号通路，促进成骨细胞分化及成骨活动；而ICG-001抑制 剂阻断了β-catenin信号通路从而减弱了LiCl对成骨细胞分化的保护作用，提示GSK-3β/β-catenin信号通路可能是介导钛磨损颗粒诱导假体周 围骨溶解的重要机制；③在体内实验中，通过应用骨硬化蛋白抗体、蛋白磷酸酶2A抑制、LiCl、AR28等方式通过激活Wnt/β-catenin等信号 通路后，进而促进成骨形成，抑制破骨吸收，增加局部骨量及骨体积，对抗钛等磨损颗粒诱导的假体周围骨溶解作用；④基因层面，在 骨硬化蛋白静默条件下，即使用钛粒子处理下MC3T3-E1细胞的活性以及矿化也明显增强；相反，减少骨硬化蛋白的表达水平反而增加了 β-catenin的表达水平；结果提示基因表达的降低可激活Wnt/β-catenin信号通路促进骨形成，改善钛颗粒引起的骨丢失。 [ABSTRACT FROM AUTHOR]

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