TY - JOUR
T1 - Berberine sulfate attenuates osteoclast differentiation through RANKL induced NF-κB and NFAT pathways
AU - Zhou, Lin
AU - Song, Fangming
AU - Liu, Qian
AU - Yang, Mingli
AU - Zhao, Jinmin
AU - Tan, Renxiang
AU - Xu, Jun
AU - ZHANG, Ge
AU - Quinn, Julian M.W.
AU - Tickner, Jennifer
AU - Xu, Jiake
N1 - Publisher Copyright:
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2015/11/13
Y1 - 2015/11/13
N2 - 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.
AB - 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.
KW - Berberine sulfate
KW - NF-κB and NFAT pathway
KW - Osteoclast
KW - RANKL
UR - http://www.scopus.com/inward/record.url?scp=84947288770&partnerID=8YFLogxK
U2 - 10.3390/ijms161125998
DO - 10.3390/ijms161125998
M3 - Journal article
C2 - 26580592
AN - SCOPUS:84947288770
SN - 1661-6596
VL - 16
SP - 27087
EP - 27096
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 11
ER -