Tereticornate A suppresses RANKL-induced osteoclastogenesis via the downregulation of c-Src and TRAF6 and the inhibition of RANK signaling pathways.

Autor: Liu T; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China., Jiang L; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China., Xiang Z; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China., Li J; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China., Zhang Y; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China., Xiang T; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China., Wang W; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China., Li X; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China., Jia Y; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China., Huang X; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China., Lu X; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China., Xu H; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China. Electronic address: xuhuan1017@163.com., Wang X; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming 650201, China. Electronic address: jwang@ynau.edu.cn., Sheng J; Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming 650201, China. Electronic address: shengj@ynau.edu.cn.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Jul; Vol. 151, pp. 113140. Date of Electronic Publication: 2022 May 20.
DOI: 10.1016/j.biopha.2022.113140
Abstrakt: Excessive osteoclast differentiation and activation are closely associated with the development and progression of osteoporosis. Natural plant-derived compounds that can inhibit osteoclastogenesis are an efficient strategy for the prevention and treatment of osteoporosis. Tereticornate A (TA) is a natural terpene ester compound extracted from the leaves and branches of Eucalyptus gracilis, with antiviral, antibacterial, and anti-inflammatory activities. However, the effect of TA on osteoclastogenesis and the underlying molecular mechanism remain unclear. Based on the key role of the NF-κB pathway in the regulation of osteoclastogenesis and the observation that TA exhibits an anti-inflammatory effect by inhibiting NF-κB activity, we speculated that TA could exert anti-osteoclastogenesis activity. Herein, TA could inhibit the RANKL-induced osteoclast differentiation and formation of F-actin rings in RAW 264.7 cells. Mechanistically, TA downregulated the expression of c-Src and TRAF6, and also suppressed the RANKL-stimulated canonical RANK signaling pathways, including AKT, MAPK (p38, JNK, and ERK), and NF-κB; ultimately, downregulating the expression of NFATc1 and c-Fos, the key transcriptional factors required for the expression of genes (e.g., TRAP, cathepsin K, β-Integrin, MMP-9, ATP6V0D2, and DC-STAMP) that govern osteoclastogenesis. Our findings demonstrated that TA could effectively inhibit RANKL-induced osteoclastogenesis via the downregulation of c-Src and TRAF6 and the inhibition of RANK signaling pathways. Thus, TA could serve as a novel osteoclastogenesis inhibitor and might have beneficial effects on bone health.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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