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Anti-osteoclastogenic activity of praeruptorin A via inhibition of p38/Akt-c-Fos-NFATc1 signaling and PLC?-independent Ca2+ oscillation.


ABSTRACT:

Background

A decrease of bone mass is a major risk factor for fracture. Several natural products have traditionally been used as herbal medicines to prevent and/or treat bone disorders including osteoporosis. Praeruptorin A is isolated from the dry root extract of Peucedanum praeruptorum Dunn and has several biological activities, but its anti-osteoporotic activity has not been studied yet.

Materials and methods

The effect of praeruptorin A on the differentiation of bone marrow-derived macrophages into osteoclasts was examined by phenotype assay and confirmed by real-time PCR and immunoblotting. The involvement of NFATc1 in the anti-osteoclastogenic action of praeruptorin A was evaluated by its lentiviral ectopic expression. Intracellular Ca(2+) levels were also measured.

Results

Praeruptorin A inhibited the RANKL-stimulated osteoclast differentiation accompanied by inhibition of p38 and Akt signaling, which could be the reason for praeruptorin A-downregulated expression levels of c-Fos and NFATc1, transcription factors that regulate osteoclast-specific genes, as well as osteoclast fusion-related molecules. The anti-osteoclastogenic effect of praeruptorin A was rescued by overexpression of NFATc1. Praeruptorin A strongly prevented the RANKL-induced Ca(2+) oscillation without any changes in the phosphorylation of PLC?.

Conclusion

Praeruptorin A could exhibit its anti-osteoclastogenic activity by inhibiting p38/Akt-c-Fos-NFATc1 signaling and PLC?-independent Ca(2+) oscillation.

SUBMITTER: Yeon JT 

PROVIDER: S-EPMC3931687 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Anti-osteoclastogenic activity of praeruptorin A via inhibition of p38/Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca2+ oscillation.

Yeon Jeong-Tae JT   Kim Kwang-Jin KJ   Choi Sik-Won SW   Moon Seong-Hee SH   Park Young Sik YS   Ryu Byung Jun BJ   Oh Jaemin J   Kim Min Seuk MS   Erkhembaatar Munkhsoyol M   Son Young-Jin YJ   Kim Seong Hwan SH  

PloS one 20140221 2


<h4>Background</h4>A decrease of bone mass is a major risk factor for fracture. Several natural products have traditionally been used as herbal medicines to prevent and/or treat bone disorders including osteoporosis. Praeruptorin A is isolated from the dry root extract of Peucedanum praeruptorum Dunn and has several biological activities, but its anti-osteoporotic activity has not been studied yet.<h4>Materials and methods</h4>The effect of praeruptorin A on the differentiation of bone marrow-de  ...[more]

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