The Coumarin Derivative 5′-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways

• Published in: BioMed research international 2019, Vol.2019 (2019), p.1-10
• Main Authors: Abdel-Moneim, Ashraf M., Badr, Gehan Moustafa, Elsawy, Hany, Ali, Enas M., Abdallah, Basem M., al-Zahrani, Abd Allah Musa M.
• Format: Article
• Language: English
• Subjects: Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; Biomedical materials; Biotechnology industry; Bone marrow; c-Fos protein; Calcium phosphates; Cell differentiation; Cell proliferation; Cell viability; Coumarin; Differentiation; Enzymatic activity; Enzyme activity; Enzymes; Gene expression; Gene regulation; Immunoglobulins; MAP kinase; NF-κB protein; Older people; Osteoblastogenesis; Osteoclastogenesis; Osteoclasts; Phosphatase; Phosphatases; Phosphorylation; Signal transduction; Signaling; Stimulators; TRANCE protein; Tumor necrosis factor-TNF
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2019/9395146

The phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5′-hydroxy auraptene (5′-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5′-HA on osteoclast differentiation of mouse bone marrow (BM) cells. The effect of 5′-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP+ multinucleated cells (TRAP+MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5′-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5′-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5′-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5′-HA in BM cells. In conclusion, we identified 5′-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.