Department of Spine Surgery, Honghui Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Department of Orthopedics, Yan'an University Medical School, Yan'an, China.
Biosci Rep. 2020 Jul 31;40(7). doi: 10.1042/BSR20200407.
Recently, Rho GTPases substrates include Rac (Rac1 and Rac2) and Cdc42 that have been reported to exert multiple cellular functions in osteoclasts, the most prominent of which includes regulating the dynamic actin cytoskeleton rearrangements. In addition, natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Although currently, there are reports about the natural product, which could play a therapeutic role in bone loss diseases (osteoporosis and osteolysis) through the regulation of Rac1/2 and Cdc42 during osteoclasts cytoskeletal structuring. There have been several excellent studies for exploring the therapeutic potentials of various natural products for their role in inhibiting cancer cells migration and function via regulating the Rac1/2 and Cdc42. Herein in this review, we try to focus on recent advancement studies for extensively understanding the role of Rho GTPases substrates Rac1, Rac2 and Cdc42 in osteoclastogenesis, as well as therapeutic potentials of natural medicinal products for their properties on the regulation of Rac1, and/or Rac2 and Cdc42, which is in order to inspire drug discovery in regulating osteoclastogenesis.
最近,Rho GTPases 的底物包括 Rac(Rac1 和 Rac2)和 Cdc42,它们被报道在破骨细胞中发挥多种细胞功能,其中最突出的包括调节动态肌动蛋白细胞骨架重排。此外,天然产物及其分子结构一直是药物化学和药物发现的有价值的起点。尽管目前有报道称,某些天然产物可能通过调节破骨细胞细胞骨架结构中的 Rac1/2 和 Cdc42,在骨丢失疾病(骨质疏松症和骨溶解)中发挥治疗作用。已经有一些优秀的研究探索了各种天然产物的治疗潜力,因为它们可以通过调节 Rac1/2 和 Cdc42 来抑制癌细胞的迁移和功能。在这篇综述中,我们试图重点关注最近的研究进展,以广泛了解 Rho GTPases 底物 Rac1、Rac2 和 Cdc42 在破骨细胞发生中的作用,以及天然药物的治疗潜力,因为它们具有调节 Rac1 和/或 Rac2 和 Cdc42 的特性,以便为调节破骨细胞发生的药物发现提供灵感。