(2S)-2′-Methoxykurarinone Inhibits Osteoclastogenesis and Bone Resorption through Down-Regulation of RANKL Signaling

• Published in: Biological & pharmaceutical bulletin Vol. 37; no. 2; pp. 255 - 261
• Main Authors: Kim, Ju-Young, Kim, Jung Young, Kim, Jeong Joong, Oh, Jaemin, Kim, Youn-Chul, Lee, Myeung Su
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-02-2014; Pharmaceutical Society of Japan
• Subjects: (2S)-2′-methoxykurarinone; Animals; Bone Marrow Cells - drug effects; bone resorption; Bone Resorption - metabolism; Bone Resorption - prevention & control; Cell Differentiation - drug effects; Down-Regulation; Flavonoids - pharmacology; Flavonoids - therapeutic use; Humans; Macrophages - drug effects; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; NFATC Transcription Factors - metabolism; Osteoblasts - metabolism; osteoclast; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoclasts - physiology; osteoporosis; Osteoprotegerin - metabolism; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Proto-Oncogene Proteins c-fos - metabolism; RANK Ligand - metabolism; Receptor Activator of Nuclear Factor-kappa B - metabolism; receptor activator of nuclear factor-κB ligand (RANKL); Signal Transduction; Sophora - chemistry
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b13-00695

(2S)-2′-Methoxykurarinone (MK), a compound isolated from the roots of Sophora flavescens, has various physiological properties, such as anti-inflammatory, antipyretic, antidiabetic, and antineoplastic effects. However, the effect of S. flavescens-derived MK on osteoclastogenesis remains unknown. Therefore, we examined the effect and mechanism of action of MK on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption. MK inhibited osteoclast differentiation in bone marrow cell–osteoblast cocultures but did not affect the RANKL-to-osteoprotegerin ratio induced by osteoclastogenic factors in osteoblasts. MK also inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages in a dose-dependent manner, without cytotoxicity. Pretreatment with MK significantly suppressed the Akt, p38, c-Jun N terminal kinase (JNK), c-Fos, and nuclear factor of activated T cells c1 (NFATc1) pathways and inhibited the bone-resorbing activity of mature osteoclasts. These results collectively suggest that MK inhibits osteoclast differentiation and bone resorption through RANKL-induced mitogen-activated protein kinases (MAPKs) and c-Fos-NFATc1 signaling pathways.