Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Korea.
Department of Food Science and Biotechnology, Daegu University, Gyeongsan 38453, Korea.
Int J Mol Sci. 2018 Feb 17;19(2):601. doi: 10.3390/ijms19020601.
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.
没食子酸丙酯，一种含苯并三唑酮的天然化合物，据报道具有多种生物学和药理学功能，如抗氧化、抗癌和抗炎作用。在本研究中，我们从焦儿茶酚酶促合成了没食子酸丙酯，并研究了其在核因子-κB 受体激活剂配体（RANKL）诱导的破骨细胞分化中的作用。没食子酸丙酯抑制了骨髓巨噬细胞（BMM）中多核抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞的形成，而没有引起细胞毒性，并抑制了破骨细胞特异性标志物的上调，包括 TRAP（Acp5）、组织蛋白酶 K（Ctsk）和树突状细胞特异性跨膜蛋白（Dcstamp）。然而，没食子酸丙酯并没有影响成熟破骨细胞的骨吸收功能，这可以通过吸收陷窝试验证明。RANK 信号转导中丝裂原活化蛋白激酶（Akt 和 IkB 途径）的激活不受没食子酸丙酯的影响，而破骨细胞分化中的关键转录调节因子 c-Fos 和 NFATc1 的表达则被没食子酸丙酯显著抑制。没食子酸丙酯还显著降低了 B 淋巴细胞诱导成熟蛋白-1（Blimp1）基因（Prdm1）的表达水平。此外，下调 Blimp1 导致抗破骨细胞基因，包括干扰素调节因子-8（Irf8）和 B 细胞淋巴瘤 6（Bcl6）基因的强制表达。总之，我们的数据表明，没食子酸丙酯通过下调 c-Fos 和 NFATc1 抑制破骨细胞分化。
