Herbal medicine Ninjinyoeito inhibits RANKL-induced osteoclast differentiation and bone resorption activity by regulating NF-κB and MAPK pathway

被引:0
作者
Htike, Kaung [1 ]
Yoshida, Kunihiro [1 ,2 ]
Eguchi, Takanori [1 ,3 ]
Takebe, Katsuki [1 ]
Li, Xueming [1 ]
Qu, Yaxin [1 ]
Sakai, Eiko [4 ]
Tsukuba, Takayuki [4 ]
Okamoto, Kuniaki [1 ]
机构
[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Dent Pharmacol, 2-5-1 Shikata Cho,Kita Ku, Okayama 7008525, Japan
[2] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral & Maxillofacial Surg, Okayama 7008525, Japan
[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Adv Res Ctr Oral & Craniofacial Sci, 2-5-1 Shikata cho,Kita ku, Okayama 7008525, Japan
[4] Nagasaki Univ, Grad Sch Biomed Sci, Dept Dent Pharmacol, 1-7-1 Sakamoto, Nagasaki 8528588, Japan
基金
日本学术振兴会;
关键词
Osteoclast; Osteoporosis; Herbal medicine Ninjinyoeito; NF-kappa B; MAP kinases; RECEPTOR ACTIVATOR; MATRIX METALLOPROTEINASES; TRANSCRIPTION FACTOR; CATHEPSIN-K; KINASE; INDUCTION; CALVARIA;
D O I
10.1016/j.job.2024.09.007
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Objectives: Osteoporosis is a systemic bone metabolism disorder characterized by decreased bone mass and strength. Osteoclasts (OCs) are giant multinucleated cells that regulate bone homeostasis by degrading bone matrix. Excessive OC differentiation and activity can lead to serious bone metabolic disorders including osteoporosis. Current treatments, including antiresorptive drugs, exert considerable adverse effects, including jaw osteonecrosis. Herbal medicines, such as Ninjinyoeito (NYT), may also offer efficacy, but with fewer adverse effects. In this study, we investigated NYT's effects on osteoclastogenesis. Methods: Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were performed to examine NYT's effects on OC differentiation and function. OC-related gene expression at mRNA and protein levels was investigated to confirm NYT's inhibitory action against osteoclastogenesis. We also demonstrated involvement of signaling pathways mediated by I kappa B alpha and mitogen-activated protein kinases (MAPK) [extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38] and showed nuclear translocation of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) and nuclear factor kappa B (NF-kappa B) p65 during osteoclastogenesis. Results: TRAP staining and bone resorption assays confirmed that NYT significantly inhibited OC differentiation and function. Western blot and RT-PCR results showed that NYT ameliorated osteoclastogenesis by suppressing mRNA and protein level expression of OC-related genes. Moreover, blots and immunocytochemistry (ICC) data clarified that NYT abrogates signaling pathways mediated by I kappa B alpha and MAPK (ERK, JNK, p38), and demonstrated nuclear translocation of NFATc1 and NF-kappa B p65 during OC differentiation. Conclusions: These findings suggest NYT is an alternative therapeutic candidate for treating osteoporosis.
引用
收藏
页码:49 / 57
页数:9
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