A paeonol derivative, YPH-PA3 promotes the differentiation of monocyte/macrophage lineage precursor cells into osteoblasts and enhances their autophagy

Chun Hao Tsai, Ming-Hua Hsu, Po Hao Huang, Chin Tung Hsieh, Ying Ming Chiu, Dong chen Shieh, Yi Ju Lee, Gregory J. Tsay, Yi Ying Wu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Previous studies have indicated that paeonol inhibits RANKL-induced osteoclastogenesis by inhibiting the ERK, p38, and NF-κB pathway. We modified paeonol to form a new compound, YPH-PA3, and found that it promoted osteoclastogenesis rather than inhibited it the way paeonol does. The aim of this study is to investigate the mechanisms involved in YPH-PA3-promoted osteoclastogenesis. YPH-PA3-promoted differentiation of RAW264.7 cells (human monocytes) into osteoclasts is activated through ERK/p38/JNK phosphorylation, affecting c-FOS, NF-κB, and NFATc2. Real-time quantitative PCR and western blot revealed an increased expression of autophagy-related markers during YPH-PA3-induced osteoclastogenesis. We also demonstrated the relationship between p62/LC3 localization and F-actin ring formation by double-labeling immunofluorescence. Knockdown of p62 small-interfering RNA (siRNA) attenuated YPH-PA3-induced expression of autophagy-related genes. Our study results indicated that p62 may play a role in YPH-PA3-induced autophagy and osteoclastogenesis, which may help to develop a novel therapeutic strategy against osteoclastogenesis-related diseases.

Original languageEnglish
Pages (from-to)104-113
Number of pages10
JournalEuropean Journal of Pharmacology
Volume832
DOIs
Publication statusPublished - 2018 Aug 5

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Monocyte-Macrophage Precursor Cells
Autophagy
Osteoblasts
Osteogenesis
Osteoclasts
Small Interfering RNA
Fluorescent Antibody Technique
paeonol
Actins
Real-Time Polymerase Chain Reaction
Monocytes
Cell Differentiation
Western Blotting
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Tsai, Chun Hao ; Hsu, Ming-Hua ; Huang, Po Hao ; Hsieh, Chin Tung ; Chiu, Ying Ming ; Shieh, Dong chen ; Lee, Yi Ju ; Tsay, Gregory J. ; Wu, Yi Ying. / A paeonol derivative, YPH-PA3 promotes the differentiation of monocyte/macrophage lineage precursor cells into osteoblasts and enhances their autophagy. In: European Journal of Pharmacology. 2018 ; Vol. 832. pp. 104-113.
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A paeonol derivative, YPH-PA3 promotes the differentiation of monocyte/macrophage lineage precursor cells into osteoblasts and enhances their autophagy. / Tsai, Chun Hao; Hsu, Ming-Hua; Huang, Po Hao; Hsieh, Chin Tung; Chiu, Ying Ming; Shieh, Dong chen; Lee, Yi Ju; Tsay, Gregory J.; Wu, Yi Ying.

In: European Journal of Pharmacology, Vol. 832, 05.08.2018, p. 104-113.

Research output: Contribution to journalArticle

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AU - Chiu, Ying Ming

AU - Shieh, Dong chen

AU - Lee, Yi Ju

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