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Rho GTPases 及其底物在破骨细胞生成中的调节作用。

The Regulatory Role of Rho GTPases and their Substrates in Osteoclastogenesis.

机构信息

Department of Spine Surgery, Honghui Hospital, School of Medicine, Xi'an Jiaotong University, China.

出版信息

Curr Drug Targets. 2021;22(9):1064-1070. doi: 10.2174/1389450121666200925150446.

Abstract

Pathological bone loss diseases (osteolysis, Paget's diseases) are commonly caused by the excessive differentiation and activity of osteoclasts. The Rho GTPases family members Rac1/2 (Rac1 and Rac2) have been reported for their special role in exerting multiple cellular functions during osteoclastic differentiation, which includes the most prominent function on dynamic actin cytoskeleton rearranging. Besides that, the increasing studies demonstrated that the regulating effects of Rac1/2 on the osteoclastic cytoskeletal organization are through the GEFs member Dock5. Although the amount of relevant studies on this topic is still limited, several excellent studies have been reported that extensively explored the molecular mechanisms involved in Rac1/2 and Dock5 during the osteoclastogenesis regulation, as well as their role as the therapeutic target in bone loss diseases. Herein, in this review, we aim to focus on recent advances studies for extensively understanding the role of Rho GTPases Rac1/2 and Dock5 in osteoclastogenesis, as well as their role as a potential therapeutic target in regulating osteoclastogenesis.

摘要

病理性骨丢失疾病(溶骨性骨病、佩吉特病)通常是由破骨细胞过度分化和活性引起的。Rho GTPases 家族成员 Rac1/2(Rac1 和 Rac2)已被报道在破骨细胞分化过程中发挥多种细胞功能方面具有特殊作用,其中包括对动态肌动蛋白细胞骨架重排的最显著作用。此外,越来越多的研究表明,Rac1/2 对破骨细胞细胞骨架组织的调节作用是通过 GEFs 成员 Dock5 实现的。尽管关于这个主题的相关研究数量仍然有限,但已经有几项优秀的研究报道广泛探讨了 Rac1/2 和 Dock5 在破骨细胞生成调节中的分子机制,以及它们作为骨丢失疾病治疗靶点的作用。在此,在这篇综述中,我们旨在重点关注最近的研究进展,以更深入地了解 Rho GTPases Rac1/2 和 Dock5 在破骨细胞生成中的作用,以及它们作为调节破骨细胞生成的潜在治疗靶点的作用。

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