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

International Journal of Molecular Sciences

Je-Yong Choi¹  Tae Hoon Kim²  Jung Eun Kim³  Hong-In Shin⁴  Eui Kyun Park⁴  Kiryeong Kim⁴  Hye Jung Ihn⁴ 

[1] Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41944, Korea;Department of Food Science and Biotechnology, Daegu University, Gyeongsan 38453, Korea;Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea;Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Korea;

关键词: purpurogallin;    RANKL;    osteoclastogenesis;    Blimp1;   

DOI  :  10.3390/ijms19020601

来源: DOAJ

【 摘 要 】

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 multinucleatedtartrate-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.

【 授权许可】

Unknown