骨溶解
破骨细胞
兰克尔
炎症
HDAC4型
NF-κB
骨吸收
癌症研究
体内
组蛋白脱乙酰基酶
化学
脂多糖
医学
药理学
内科学
内分泌学
激活剂(遗传学)
生物
受体
生物化学
组蛋白
生物技术
外科
基因
作者
Chongwei Chen,Sujing Zong,Zhenyu Wang,Ruijia Yang,Yanjing Guo,Yunfei Wang,Xinping Chen,Yue Li,Shaowei Wang
摘要
Osteoclast (OC) abnormalities lead to many osteolytic diseases, such as osteoporosis, inflammatory bone erosion, and tumor-induced osteolysis. Exploring effective strategies to remediate OCs dysregulation is essential. FTY720, also known as fingolimod, has been approved for the treatment of multiple sclerosis and has anti-inflammatory and immunosuppressive effects. Here, we found that FTY720 inhibited osteoclastogenesis and OC function by inhibiting nuclear factor kappa-B (NF-κB) signaling. Interestingly, we also found that FTY720 inhibited osteoclastogenesis by upregulating histone deacetylase 4 (HDAC4) expression levels and downregulating activating transcription factor 4 (ATF4) expression levels. In vivo, FTY720 treatment prevented lipopolysaccharide- (LPS-) induced calvarial osteolysis and significantly reduced the number of tartrate-resistant acid phosphatase- (TRAP-) positive OCs. Taken together, these results demonstrate that FTY720 can inhibit osteoclastogenesis and ameliorate inflammation-induced bone loss. Which may provide evidence of a new therapeutic target for skeletal diseases caused by OC abnormalities.
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