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 language | English |
|---|---|
| Pages (from-to) | 104-113 |
| Number of pages | 10 |
| Journal | European Journal of Pharmacology |
| Volume | 832 |
| DOIs | |
| Publication status | Published - 2018 Aug 5 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
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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 journal › Article
TY - JOUR
T1 - A paeonol derivative, YPH-PA3 promotes the differentiation of monocyte/macrophage lineage precursor cells into osteoblasts and enhances their autophagy
AU - Tsai, Chun Hao
AU - Hsu, Ming-Hua
AU - Huang, Po Hao
AU - Hsieh, Chin Tung
AU - Chiu, Ying Ming
AU - Shieh, Dong chen
AU - Lee, Yi Ju
AU - Tsay, Gregory J.
AU - Wu, Yi Ying
PY - 2018/8/5
Y1 - 2018/8/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047246215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047246215&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2018.05.024
DO - 10.1016/j.ejphar.2018.05.024
M3 - Article
C2 - 29782859
AN - SCOPUS:85047246215
VL - 832
SP - 104
EP - 113
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
ER -