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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 Complement Altern Med. 2015 Aug 14; 15:280.BC

Abstract

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.

Authors+Show Affiliations

Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea. Center for Metabolic Function Regulation, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea.Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea.Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea.Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea.Division of Rheumatology, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea. Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea. Imaging Science based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, 570-749, Republic of Korea.Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea. jmoh@wku.ac.kr. Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea. jmoh@wku.ac.kr. Imaging Science based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, 570-749, Republic of Korea. jmoh@wku.ac.kr.Imaging Science based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, 570-749, Republic of Korea. kimjy1014@gmail.com.

Pub Type(s)

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

Language

eng

PubMed ID

26271279

Citation

Cheon, Yoon-Hee, et al. "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, vol. 15, 2015, p. 280.
Cheon YH, Baek JM, Park SH, et al. 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 Complement Altern Med. 2015;15:280.
Cheon, Y. H., Baek, J. M., Park, S. H., Ahn, S. J., Lee, M. S., Oh, J., & Kim, J. Y. (2015). 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, 15, 280. https://doi.org/10.1186/s12906-015-0801-6
Cheon YH, et al. 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 Complement Altern Med. 2015 Aug 14;15:280. PubMed PMID: 26271279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Cheon,Yoon-Hee, AU - Baek,Jong Min, AU - Park,Sun-Hyang, AU - Ahn,Sung-Jun, AU - Lee,Myeung Su, AU - Oh,Jaemin, AU - Kim,Ju-Young, Y1 - 2015/08/14/ PY - 2015/06/02/received PY - 2015/08/03/accepted PY - 2015/8/15/entrez PY - 2015/8/15/pubmed PY - 2016/2/13/medline SP - 280 EP - 280 JF - BMC complementary and alternative medicine JO - BMC Complement Altern Med VL - 15 N2 - 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. SN - 1472-6882 UR - https://www.unboundmedicine.com/medline/citation/26271279/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_ L2 - https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-015-0801-6 DB - PRIME DP - Unbound Medicine ER -