Punicalagin attenuates osteoclast differentiation by impairing NFATcl expression and blocking Akt- and JNK-dependent pathways
Punicalagin attenuates osteoclast differentiation by impairing NFATcl expression and blocking Akt- and JNK-dependent pathways
复制标题
安石榴苷通过损害 NFATcl 表达并阻断 Akt 和 JNK 依赖性途径来减弱破骨细胞分化
DOI：
10.1007/s11010-015-2466-3
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发表时间：
2015
影响因子：
4.3
通讯作者：
Takashi Tanaka and Takayuki Tsukuba
中科院分区：
文献类型：
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作者：
Mayumi Iwatake;Kuniaki Okamoto;Takashi Tanaka and Takayuki Tsukuba
Punicalagin是一种具有生物活性的多酚，被归类为elagitanin。尽管已证实其具有抗氧化、抗炎、抗肿瘤等多种药理作用，但有关其对破骨细胞(OCL)的作用尚未见报道。本研究通过小鼠单核细胞RAW-D细胞株和骨髓源性巨噬细胞(BMMS)核因子kappaB受体激活剂，观察了Pucicalagin对OCL分化的影响。用Punicalagin治疗可显著抑制RAW-D细胞和BMMS的OCL形成，并阻止BMM来源的OCL的骨吸收。此外，Punicalagin可抑制OCL的多核和肌动蛋白环的形成，并降低OCL分化的主要调节因子-活化T细胞胞浆核因子-1(NFATc1)的蛋白水平，同时降低受NFATc1转录调控的Src和组织蛋白K的表达水平。Punicalagin对BMMS OCL分化过程中细胞内信号转导的影响表明，与未处理的OCLs相比，Punicalagin处理的OCLs Jun氨基末端激酶和Akt的磷酸化明显降低，细胞外信号调节激酶、p38丝裂原激活的蛋白激酶和核因子-kappa-Bα抑制物的磷酸化部分减弱。因此，Punicalagin可能通过抑制OCL分化而影响骨代谢。
Punicalagin is a bioactive polyphenol that is classified as an ellagitannin. Although punicalagin has been shown to have various pharmacological effects, such as anti-oxidative, anti-inflammatory, and anti-tumor effects, no studies have reported the effects of punicalagin on osteoclasts (OCLs). In this study, we investigated the effects of punicalagin on OCL differentiation by receptor activator of nuclear factor kappa-B ligand in the murine monocytic RAW-D cell line and bone marrow-derived macrophages (BMMs). Treatment with punicalagin significantly inhibited OCL formation from RAW-D cells and BMMs and prevented bone resorption of BMM-derived OCLs. Moreover, punicalagin impaired multinucleation and actin-ring formation in OCLs, and decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), which is a master regulator of OCL differentiation, and concomitantly reduced the expression levels of Src and cathepsin K, which are transcriptionally regulated by NFATc1. The effects of punicalagin on intracellular signaling during the OCL differentiation of BMMs indicated that punicalagin-treated OCLs displayed markedly reduced phosphorylation of Jun N-terminal kinase and Akt, and partially impaired phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and inhibitor of nuclear factor kappa-B alpha compared with untreated OCLs. Thus, punicalagin may affect bone metabolism by inhibiting OCL differentiation.