Berberine sulfate attenuates osteoclast differentiation through RANKL induced NF-κB and NFAT pathways

Lin Zhou, Fangming Song, Qian Liu, Mingli Yang, Jinmin Zhao, Renxiang Tan, Jun Xu, Ge ZHANG, Julian M.W. Quinn, Jennifer Tickner, Jiake Xu*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

26 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)27087-27096
Number of pages10
JournalInternational Journal of Molecular Sciences
Issue number11
Publication statusPublished - 13 Nov 2015

Scopus Subject Areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

User-Defined Keywords

  • Berberine sulfate
  • NF-κB and NFAT pathway
  • Osteoclast


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