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Int. J. Mol. Sci. 2018, 19(2), 601; https://doi.org/10.3390/ijms19020601

Inhibitory Effect of Purpurogallin on Osteoclast Differentiation in Vitro through the Downregulation of c-Fos and NFATc1

1
Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Korea
2
Department of Food Science and Biotechnology, Daegu University, Gyeongsan 38453, Korea
3
Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea
4
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41944, Korea
*
Author to whom correspondence should be addressed.
Received: 24 January 2018 / Revised: 12 February 2018 / Accepted: 14 February 2018 / Published: 17 February 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp). However, purpurogallin did not affect the bone resorbing function of mature osteoclasts evident by the resorption pit assay. Activation of mitogen-activated protein kinases, Akt and IkB pathways in RANK signaling were not altered by purpurogallin, whereas the expression of c-Fos and NFATc1, key transcriptional regulators in osteoclastogenesis, was dramatically inhibited by purpurogallin. Purpurogallin also significantly reduced the expression level of B lymphocyte-induced maturation protein-1 (Blimp1) gene (Prdm1). Further, downregulation of Blimp1 led to forced expression of anti-osteoclastogenic genes, including interferon regulatory factor-8 (Irf8) and B-cell lymphoma 6 (Bcl6) genes. Taken together, our data suggested that purpurogallin inhibits osteoclast differentiation via downregulation of c-Fos and NFATc1. View Full-Text
Keywords: purpurogallin; RANKL; osteoclastogenesis; Blimp1 purpurogallin; RANKL; osteoclastogenesis; Blimp1
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Kim, K.; Kim, T.H.; Ihn, H.J.; Kim, J.E.; Choi, J.-Y.; Shin, H.-I.; Park, E.K. Inhibitory Effect of Purpurogallin on Osteoclast Differentiation in Vitro through the Downregulation of c-Fos and NFATc1. Int. J. Mol. Sci. 2018, 19, 601.

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