Berberine sulfate attenuates osteoclast differentiation through RANKL induced NF-ÎºB and NFAT pathways
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 muM 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-kappaB and NFAT activity. Taken together, our results suggest that berberine sulfate is a natural compound potentially useful for the treatment of osteoporosis.
|ISBN||1422-0067 (Electronic) 1422-0067 (Linking)|
|Authors||Zhou, L.; Song, F.; Liu, Q.; Yang, M.; Zhao, J.; Tan, R.; Xu, J.; Zhang, G.; Quinn, J. M.; Tickner, J.; Xu, J.;|
|Responsible Garvan Author|
|Publisher Name||INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/26580592|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13360|