Inamitsu Hiroyuki, Okamoto Kuniaki, Sakai Eiko, Nishishita Kazuhisa, Murata Hiroshi, Tsukuba Takayuki
Department of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 852-8588, Japan.
Department of Prosthetic Dentistry, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 852-8588, Japan.
J Appl Toxicol. 2017 Jul;37(7):817-824. doi: 10.1002/jat.3429. Epub 2017 Jan 26.
The dental resin monomers 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) are released from the resin matrix due to unpolymerized monomers; once released, they influence various biological functions and the viability of cells in the oral environment. Although HEMA and TEGDMA have various effects on cells, including inflammation, inhibition of cell proliferation or differentiation, and apoptosis, the effects of these monomers on osteoclasts remain unknown. In this study, we investigated the effects of HEMA and TEGDMA on osteoclast differentiation of bone marrow-derived macrophages or murine monocytic cell line RAW-D. Both HEMA and TEGDMA inhibited osteoclast formation and their bone-resorbing activity at non-cytotoxic concentrations. Moreover, HEMA and TEGDMA decreased the expression of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), a master regulator of osteoclast differentiation, and of osteoclast markers that are transcriptionally regulated by NFATc1, including Src and cathepsin K. Regarding their effects on signaling pathways involved in osteoclast differentiation, HEMA impaired the phosphorylation of extracellular signal-regulated kinase and Jun N-terminal kinase, whereas TEGDMA attenuated the phosphorylation of Akt and Jun N-terminal kinase. Thus, HEMA and TEGDMA inhibit osteoclast differentiation through different signaling pathways. This is the first report on the effects of the monomers HEMA and TEGDMA on osteoclasts. Copyright © 2017 John Wiley & Sons, Ltd.
牙科树脂单体甲基丙烯酸2-羟乙酯（HEMA）和二甲基丙烯酸三甘醇酯（TEGDMA）会因未聚合的单体从树脂基质中释放出来；一旦释放，它们会影响口腔环境中各种生物学功能和细胞活力。尽管HEMA和TEGDMA对细胞有多种影响，包括炎症、抑制细胞增殖或分化以及诱导凋亡，但这些单体对破骨细胞的影响仍不清楚。在本研究中，我们调查了HEMA和TEGDMA对骨髓来源的巨噬细胞或小鼠单核细胞系RAW-D破骨细胞分化的影响。在无细胞毒性浓度下，HEMA和TEGDMA均抑制破骨细胞形成及其骨吸收活性。此外，HEMA和TEGDMA降低了活化T细胞核因子胞质1（NFATc1）的表达，NFATc1是破骨细胞分化的主要调节因子，同时也降低了受NFATc1转录调控的破骨细胞标志物的表达，包括Src和组织蛋白酶K。关于它们对破骨细胞分化相关信号通路的影响，HEMA损害了细胞外信号调节激酶和Jun N端激酶的磷酸化，而TEGDMA减弱了Akt和Jun N端激酶的磷酸化。因此，HEMA和TEGDMA通过不同的信号通路抑制破骨细胞分化。这是关于单体HEMA和TEGDMA对破骨细胞影响的首次报道。版权所有© 2017约翰威立父子有限公司。
