Suppressive effects of (-)-tubaic acid on RANKL-induced osteoclast differentiation and bone resorption

Soomin Lim; Hye Jung Ihn; Ju Ang Kim; Jong-Sup Bae; Jung-Eun Kim; Yong Chul Bae; Hong-In Shin; Tae Hoon Kim; Eui Kyun Park

doi:10.1080/19768354.2023.2166107

Suppressive effects of (-)-tubaic acid on RANKL-induced osteoclast differentiation and bone resorption

Anim Cells Syst (Seoul). 2023 Jan 12;27(1):1-9. doi: 10.1080/19768354.2023.2166107. eCollection 2023.

Authors

Soomin Lim¹, Hye Jung Ihn², Ju Ang Kim¹, Jong-Sup Bae³, Jung-Eun Kim⁴, Yong Chul Bae⁵, Hong-In Shin¹, Tae Hoon Kim⁶, Eui Kyun Park¹

Affiliations

¹ Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea.
² Cell and Matrix Research Institute (CMRI), Kyungpook National University, Daegu, Republic of Korea.
³ College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea.
⁴ Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
⁵ Department of Oral Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
⁶ Department of Food Science and Biotechnology, Daegu University, Gyeongsan, Republic of Korea.

Abstract

Regulation of osteoclastogenesis and bone-resorbing activity can be an efficacious strategy for treating bone loss diseases because excessive osteoclastic bone resorption leads to the development of such diseases. Here, we investigated the role of (-)-tubaic acid, a thermal degradation product of rotenone, in osteoclast formation and function in an attempt to identify alternative natural compounds. (-)-Tubaic acid significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation at both the early and late stages, suggesting that (-)-tubaic acid affects the commitment and differentiation of osteoclast progenitors as well as the cell-cell fusion of mononuclear osteoclasts. (-)-Tubaic acid attenuated the activation of extracellular signal-regulated kinase (ERK) and expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and its target genes in response to RANKL. Furthermore, a pit-formation assay revealed that (-)-tubaic acid significantly impaired the bone-resorbing activity of osteoclasts. Our results demonstrated that (-)-tubaic acid exhibits anti-osteoclastogenic and anti-resorptive effects, indicating its therapeutic potential in the management of osteoclast-related bone diseases.

Keywords: (-)-tubaic acid; bone resorption; nuclear factor of activated T-cells cytoplasmic 1 (NFATc1); osteoclast.

Grants and funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT): [Grant Number 2017R1A5A2015391, 2020M3A9I4039539].