Anti-Osteoclastogenic Activity of Praeruptorin A via Inhibition of p38/Akt-c-Fos-NFATc1 Signaling and PLC gamma-Independent Ca2+ Oscillation

作者：Yeon Jeong Tae; Kim Kwang Jin; Choi Sik Won; Moon Seong Hee; Park Young Sik; Ryu Byung Jun; Oh Jaemin; Kim Min Seuk; Erkhembaatar Munkhsoyol; Son Young Jin^*; Kim Seong Hwan

来源：PLos One, 2014, 9(2): e88974.

DOI：10.1371/journal.pone.0088974

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. %26lt;br%26gt;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 Ca2+ levels were also measured. %26lt;br%26gt;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 Ca2+ oscillation without any changes in the phosphorylation of PLCc. %26lt;br%26gt;Conclusion: Praeruptorin A could exhibit its anti-osteoclastogenic activity by inhibiting p38/Akt-c-Fos-NFATc1 signaling and PLCc-independent Ca2+ oscillation.

• 出版日期2014-2-21