2,5-Dihydroxyacetophenone attenuates RANKL-mediated osteoclastogenesis by affecting the NFATc1 signaling pathway in vitro

Hai-Wei Chen; Chi-Fen Chen; Pei-Rong Lee; Shuenn-Jium Yiin; Jia-Yun Liang; Jue-Liang Hsu; Chi-I Chang; Chi-Liang Chern

doi:10.1016/j.bmcl.2023.129500

2,5-Dihydroxyacetophenone attenuates RANKL-mediated osteoclastogenesis by affecting the NFATc1 signaling pathway in vitro

Bioorg Med Chem Lett. 2023 Oct 27:129500. doi: 10.1016/j.bmcl.2023.129500. Online ahead of print.

Authors

Hai-Wei Chen¹, Chi-Fen Chen², Pei-Rong Lee³, Shuenn-Jium Yiin⁴, Jia-Yun Liang⁵, Jue-Liang Hsu⁶, Chi-I Chang⁷, Chi-Liang Chern⁸

Affiliations

¹ Department of Orthopedic Surgery, Fooyin University Hospital, Pingtung 92849, Taiwan; Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan.
² Department of Laboratory Medicine, Yuan's General Hospital, Kaohsiung 80249, Taiwan.
³ Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan; Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan.
⁴ Department of Nursing, National Tainan Junior College of Nursing, Tainan 70043, Taiwan.
⁵ Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan.
⁶ Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
⁷ Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan. Electronic address: changchii@mail.npust.edu.tw.
⁸ Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan. Electronic address: mt115@fy.edu.tw.

PMID: 39491119
DOI: 10.1016/j.bmcl.2023.129500

Abstract

Excessive bone resorption activity of osteoclasts is a common characteristic of osteolytic conditions such as osteoporosis and inflammatory bone diseases. Natural compounds with antiosteoclastogenic function seem to be beneficial for the treatment of osteolytic diseases. In this study, we evaluated the effects of 2,5-dihydroxyacetophenone (DHAP), a phenolic compound in Ganoderma bambusicola, on osteoclastogenesis induced in vitro by the receptor activator of nuclear factor-κB ligand (RANKL). DHAP inhibited the differentiation, actin ring formation, and bone resorption activity of osteoclasts. In particular, DHAP inhibited the transcriptional activity of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) during osteoclastogenesis. This inhibition resulted in reduced expression levels of cathepsin k (Ctsk), tartrate-resistant acid phosphatase (Trap), and NFATc1 (Nfatc1), thereby reducing the differentiation of osteoclasts. However, DHAP did not affect reactive oxygen species production or activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) signaling. Our findings suggest that DHAP inhibits RANKL-induced osteoclastogenesis by inhibiting the NFATc1 signaling pathway.

Keywords: 2,5-Dihydroxyacetophenone; Antiosteoclastogenesis; Ganoderma bambusicola; NFATc1; RANKL.