FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF- κ B and HDAC4/ATF Pathways.
Chongwei ChenSujing ZongZhenyu WangRuijia YangYanjing GuoYunfei WangXinping ChenYue LiShaowei WangPublished in: Journal of immunology research (2023)
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.
Keyphrases
- lps induced
- bone loss
- nuclear factor
- inflammatory response
- histone deacetylase
- multiple sclerosis
- transcription factor
- toll like receptor
- signaling pathway
- oxidative stress
- poor prognosis
- high glucose
- diabetic rats
- bone mineral density
- binding protein
- endoplasmic reticulum stress
- postmenopausal women
- cell proliferation
- endothelial cells
- long non coding rna
- replacement therapy