FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-κB and HDAC4/ATF Pathways. (6th January 2023)

• Record Type: Journal Article
• Authors: Chen, Chongwei; Zong, Sujing; Wang, Zhenyu; Yang, Ruijia; Guo, Yanjing; Wang, Yunfei; Chen, Xinping; Li, Yue; Wang, Shaowei
• Other Names: Xu Baohui Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2023(2023)
• Publication Date: 2023-01-06
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2023/8571649
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : 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- κ B) 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.