Momordin I, an inhibitor of AP-1, suppressed osteoclastogenesis through inhibition of NF-κB and AP-1 and also reduced osteoclast activity and survival
Osteoclasts originating from hematopoietic precursor cells differentiate into multinucleated cells through multiple steps. The essential roles of NF-κB and AP-1 in osteoclast differentiation have been clearly demonstrated in numerous studies. c-Fos, a component of AP-1 transcription factor, plays a...
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Published in | Biochemical and biophysical research communications Vol. 337; no. 3; pp. 815 - 823 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
25.11.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Osteoclasts originating from hematopoietic precursor cells differentiate into multinucleated cells through multiple steps. The essential roles of NF-κB and AP-1 in osteoclast differentiation have been clearly demonstrated in numerous studies. c-Fos, a component of AP-1 transcription factor, plays a key role in osteoclast differentiation. Recently, we found a strong inhibitor of AP-1 transcriptional activity, named momordin I, based on the structure of oleanolic acid glycosides and originally isolated from
Ampelopsis radix. So, we hypothesized that momordin I might be able to regulate osteoclast formation, activity, and survival. Here, we report the ability of momordin I to suppress osteoclastogenesis in a co-cultured system and a RANKL-induced osteoclast precursor system. Momordin I remarkably inhibited the activation of NF-κB as well as AP-1 in RANKL-induced RAW264.7 cells, in which momordin I appeared to target IκB degradation and c-Fos expression, respectively, but not MAPK signaling pathways. The ability of momordin I to change the ratio of RANKL and OPG in primary osteoblasts was partially responsible for the reduction of osteoclast formation. Furthermore, pit formation on dentin slices was suppressed by momordin I with stimulating actin ring disruption. Our results also showed that momordin I highly shortened osteoclast lifespan and induced osteoclast apoptosis. In conclusion, the present results demonstrate for the first time that momordin I is a potent inhibitor of osteoclast differentiation via the reduction of NF-κB and AP-1, and also suppresses osteoclast function and survival. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2005.09.113 |