The Coffee Diterpene Kahweol Prevents Osteoclastogenesis via Impairment of NFATc1 Expression and Blocking of Erk Phosphorylation
The Coffee Diterpene Kahweol Prevents Osteoclastogenesis via Impairment of NFATc1 Expression and Blocking of Erk Phosphorylation
复制标题
DOI：
10.1254/jphs.11212fp
复制
发表时间：
2012-04-01
影响因子：
3.5
通讯作者：
Tsukuba, Takayuki
中科院分区：
文献类型：
--
作者：
Fumimoto, Reiko;Sakai, Eiko;Tsukuba, Takayuki
破骨细胞（OCL）是一种多核骨吸收细胞，其分化受核因子κ B受体激活因子配体（RANKL）和巨噬细胞集落刺激因子（M-CSF）的调节。已知炎性细胞因子和氧化应激刺激OCL的分化。在这里，我们评估了咖啡豆酚，一种咖啡特异性二萜，据报道具有抗氧化和抗炎特性，对骨髓源性巨噬细胞（BCLs）或鼠单核细胞系RAW-D细胞分化为OCL的影响。Kahweol剂量依赖性地抑制Bcadium和RAW-D细胞中抗酒石酸酸性磷酸酶染色阳性OCL的形成。此外，kahweol阻止OCL的骨吸收活性。Kahweol完全消除RANKL刺激的细胞外信号调节激酶磷酸化和受损的Akt磷酸化。此外，蛋白水平的活化T细胞的核因子胞质-1（NFATc 1），一个主调节OCL分化;和OCL标记物转录调节NFATc 1如Src和组织蛋白酶K下调kahweol治疗。作为kahweol抑制作用的分子机制之一，我们还表明，kahweol上调血红素加氧酶-1和抑制高迁移率族蛋白盒I的释放。因此，咖啡中的咖啡酚是抑制OCL分化的有用成分。
Osteoclasts (OCLs) are multinucleated bone resorbing cells whose differentiation is regulated by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). It is known that inflammatory cytokines and oxidative stress stimulate differentiation of OCLs. Here we evaluated the effects of kahweol, a coffee-specific diterpene, which has been reported to possess anti-oxidant and anti-inflammatory properties, on the differentiation of bone marrow derived macrophages (BMMs) or murine monocytic cell line RAW-D cells into OCLs. Kahweol dose-dependently inhibited the formation of tartrate-resistant acid phosphatase staining positive OCLs from both BMMs and RAW-D cells. In addition, kahweol prevented the bone resorbing activity of OCLs. Kahweol completely abolished RANKL-stimulated phosphorylation of extracellular signal-regulated kinase and impaired phosphorylation of Akt. Moreover, the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), a master regulator for OCL differentiation; and OCL markers transcriptionally regulated by NFATc1 such as Src and cathepsin K were down-regulated by kahweol treatment. As one of the molecular mechanisms for the inhibitory effects of kahweol, we also showed that kahweol up-regulated heme oxygenase-1 and inhibited high mobility group box I release. Thus, kahweol in coffee is a useful constituent for inhibition of OCL differentiation.