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

Yuan Liu,Baorong He,Liang Yan,Yusheng Dou,Wanli Smith,Xiaobin Yang,Lingbo Kong

doi:10.1042/bsr20200407

Yuan Liu, Baorong He + Show 5 more

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https://doi.org/10.1042/bsr20200407

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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.

Highlights

Osteoclastogenesis has been defined as a multistep processes of osteoclast differentiation [1], including several osteoclastic cellular biological functions; such as: migration, cellular contact, cellular fusion and cellular response extracellular factors [2]
Documented studies demonstrated that osteoclastogenesis initially mediated by two critical cytokines, the macrophage colony stimulating factor-1 (M-CSF) and the receptor activator of nuclear factor-κB ligand (RANKL) [3]
M-CSF binds to its receptor present in osteoclast precursors, which stimulates their proliferation and inhibits their apoptosis; while, RANKL interacts with its receptor RANK in osteoclast precursor cells, and osteoclastognesis is induced [4] (Figure 1)

Summary

Introduction

Osteoclastogenesis has been defined as a multistep processes of osteoclast differentiation [1], including several osteoclastic cellular biological functions; such as: migration, cellular contact, cellular fusion and cellular response extracellular factors [2]. There have been no reports on 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 exploring the therapeutic potentials of various natural products in regulating cancer cells migration and function (Table 1).

Results

Conclusion