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Int. J. Mol. Sci. 2015, 16(11), 27087-27096; doi:10.3390/ijms161125998

Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-κB and NFAT Pathways

1
School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, WA 6009, Australia
2
Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning 530021, China
3
Pharmaceutical college, Guangxi Medical University, Nanning 530021, China
4
Department of Orthopaedic Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
5
Institute of Functional Biomolecules, Medical School, Nanjing University, Nanjing 210093, China
6
Research Center for Drug Discovery (RCDD), School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle at University City, Guangzhou 510006, China
7
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
8
The Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: Aiping Lu, Charles J. Malemud and Ge Zhang
Received: 3 September 2015 / Revised: 21 October 2015 / Accepted: 3 November 2015 / Published: 13 November 2015
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Abstract

Osteoporosis, a metabolic bone disease, is characterized by an excessive formation and activation of osteoclasts. Anti-catabolic treatment using natural compounds has been proposed as a potential therapeutic strategy against the osteoclast related osteolytic diseases. In this study, the activity of berberine sulfate (an orally available form of berberine) on osteoclast differentiation and its underlying molecular mechanisms of action were investigated. Using bone marrow macrophages (BMMs) derived osteoclast culture system, we showed that berberine sulfate at the dose of 0.25, 0.5 and 1 μM significantly inhibited the formation of osteoclasts. Notably, berberine sulfate at these doses did not affect the BMM viability. In addition, we observed that berberine sulfate inhibited the expression of osteoclast marker genes, including cathepsin K (Ctsk), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP, Acp5) and Vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2). Luciferase reporter gene assay and Western blot analysis further revealed that berberine sulfate inhibits receptor for activation of nuclear factor ligand (RANKL)-induced NF-κB and NFAT activity. Taken together, our results suggest that berberine sulfate is a natural compound potentially useful for the treatment of osteoporosis. View Full-Text
Keywords: berberine sulfate; osteoclast; RANKL; NF-κB and NFAT pathway berberine sulfate; osteoclast; RANKL; NF-κB and NFAT pathway
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Zhou, L.; Song, F.; Liu, Q.; Yang, M.; Zhao, J.; Tan, R.; Xu, J.; Zhang, G.; Quinn, J.M.W.; Tickner, J.; Xu, J. Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-κB and NFAT Pathways. Int. J. Mol. Sci. 2015, 16, 27087-27096.

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