Inhibitory effects of methyl-3,5-di-O-caffeoyl-epi-quinate on RANKL-induced osteoclast differentiation

Tae Hoon Kim; Hye Jung Ihn; Kiryeong Kim; Hye-Sung Cho; Hong-In Shin; Yong Chul Bae; Eui Kyun Park

doi:10.1016/j.bmcl.2018.03.072

Inhibitory effects of methyl-3,5-di-O-caffeoyl-epi-quinate on RANKL-induced osteoclast differentiation

Bioorg Med Chem Lett. 2018 Jun 1;28(10):1925-1930. doi: 10.1016/j.bmcl.2018.03.072. Epub 2018 Apr 9.

Authors

Tae Hoon Kim¹, Hye Jung Ihn², Kiryeong Kim³, Hye-Sung Cho³, Hong-In Shin³, Yong Chul Bae⁴, Eui Kyun Park⁵

Affiliations

¹ Department of Food Science and Biotechnology, Daegu University, Gyeongsan 38453, Republic of Korea.
² IHBR, Kyungpook National University, Daegu 41940, Republic of Korea.
³ Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Republic of Korea.
⁴ Department of Oral Anatomy and Neuroscience, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea.
⁵ Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Republic of Korea. Electronic address: epark@knu.ac.kr.

PMID: 29657104
DOI: 10.1016/j.bmcl.2018.03.072

Abstract

In this study, we have shown that methyl-3,5-di-O-caffeoyl-epi-quinate, a naturally occurring compound isolated from Ainsliaea acerifolia, inhibits receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and the expression of osteoclast marker genes. Methyl-3,5-di-O-caffeoyl-epi-quinate also inhibited RANKL-induced activation of p38, Akt and extracellular signal-regulated kinase (ERK) as well as the expression of nuclear factor of activated T-cell (NFATc1), the key regulator of osteoclast differentiation. Negative regulators for osteoclast differentiation was upregulated by methyl-3,5-di-O-caffeoyl-epi-quinate. Collectively, our results suggested that methyl-3,5-di-O-caffeoyl-epi-quinate suppresses osteoclast differentiation via downregulation of RANK signaling pathways and NFATc1.

Keywords: Differentiation; Methyl-3,5-di-O-caffeoyl-epi-quinate; NFATc1; Osteoclast.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asteraceae / chemistry
Asteraceae / metabolism
Bone Marrow Cells / cytology
Cell Differentiation / drug effects*
Cell Line
Down-Regulation / drug effects
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / metabolism
Interferon Regulatory Factors / metabolism
Macrophages / cytology
Macrophages / drug effects
Macrophages / metabolism
Mice
NFATC Transcription Factors / metabolism
Osteoclasts / cytology
Osteoclasts / metabolism
Quinic Acid / analogs & derivatives*
Quinic Acid / chemistry*
Quinic Acid / isolation & purification
Quinic Acid / pharmacology
RANK Ligand / pharmacology*
Signal Transduction / drug effects
Up-Regulation / drug effects

Substances

Interferon Regulatory Factors
NFATC Transcription Factors
Nfatc1 protein, mouse
RANK Ligand
interferon regulatory factor-8
methyl-3,5-di-O-caffeoyl-epi-quinate
Quinic Acid
Extracellular Signal-Regulated MAP Kinases