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

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4 Citations (Scopus)


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
Publication statusPublished - 2018 Aug 5


All Science Journal Classification (ASJC) codes

  • Pharmacology

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