The role of Rho GTPases' substrates Rac and Cdc42 in osteoclastogenesis and relevant natural medicinal products study

Biosci Rep. 2020 Jul 31;40(7):BSR20200407. doi: 10.1042/BSR20200407.

Abstract

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.

Keywords: Cdc42; Rac; Rac1; Rho GTPase; bone; natural compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Biological Products / pharmacology*
  • Biological Products / therapeutic use
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Drug Discovery
  • Humans
  • Models, Animal
  • Molecular Targeted Therapy / methods
  • Osteoblasts / drug effects
  • Osteoblasts / physiology
  • Osteoclasts / drug effects
  • Osteoclasts / pathology
  • Osteogenesis / drug effects*
  • Osteolysis / drug therapy
  • Osteolysis / pathology
  • Osteoporosis / drug therapy
  • Osteoporosis / pathology
  • RAC2 GTP-Binding Protein
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • cdc42 GTP-Binding Protein / antagonists & inhibitors
  • cdc42 GTP-Binding Protein / metabolism*
  • rac GTP-Binding Proteins / antagonists & inhibitors
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein / antagonists & inhibitors
  • rac1 GTP-Binding Protein / metabolism*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Biological Products
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins