Stauntonia hexaphylla (Lardizabalaceae) leaf methanol extract inhibits osteoclastogenesis and bone resorption activity via proteasome-mediated degradation of c-Fos protein and suppression of NFATc1 expression

BMC Complementary and Alternative Medicine

Ju-Young Kim³  Jaemin Oh³  Myeung Su Lee³  Sung-Jun Ahn¹  Sun-Hyang Park¹  Jong Min Baek¹  Yoon-Hee Cheon² 

[1]Department of Anatomy, School of Medicine, Wonkwang University, Iksan 570-749, Jeonbuk, Republic of Korea

[2]Center for Metabolic Function Regulation, Wonkwang University, Iksan 570-749, Jeonbuk, Republic of Korea

[3]Imaging Science based Lung and Bone Diseases Research Center, Wonkwang University, Iksan 570-749, Republic of Korea

关键词: Bone resorption;    NFATc1;    c-Fos;    Osteoclast;    Stauntonia hexaphylla;   

Others  :  1222549
DOI  :  10.1186/s12906-015-0801-6

 received in 2015-06-02, accepted in 2015-08-03,  发布年份 2015

【 摘 要 】

Background

Natural plants, including common vegetables and fruits, have been recognized as essential sources for drug discovery and the development of new, safe, and economical medicaments. Stauntonia hexaphylla (Lardizabalaceae) is widely distributed in Korea, Japan, and China, and is a popular herbal supplement in Korean and Chinese folk medicine owing to its analgesic, sedative, and diuretic properties. However, the exact pharmacological effects of S. hexaphylla extract, particularly its effect on osteoclastogenesis, are not known.

Methods

Osteoclast differentiation and function were identified with tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay, and the underling mechanisms were determined by real-time RT-PCR and western blot analysis.

Results

S. hexaphylla was found to inhibit early-stage receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs) without cytotoxicity and bone-resorbing activity in mature osteoclasts in a dose-dependent manner. This S. hexaphylla-mediated blockade of osteoclastogenesis involved abrogation of the NF-κB, ERK, and c-Src-Btk-PLCγ2 calcium signal pathways. Interestingly, we found that S. hexaphylla down-regulated RANKL-associated c-Fos protein induction by suppressing its translation. Furthermore, ectopic overexpression of c-Fos and NFATc1 rescued the inhibition of osteoclast differentiation by S. hexaphylla. Furthermore, S. hexaphylla inhibited the c-Fos- and NFATc1-regulated expression of genes required for osteoclastogenesis, such as TRAP, OSCAR, β3-integrin, ATP6v0d2, and CtsK.

Conclusions

These findings suggest that S. hexaphylla might be useful for the development of new anti-osteoporosis agents.

【 授权许可】

   
2015 Cheon et al.

【 图 表 】

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