TLR4 inhibition ameliorated glucolipotoxicity-induced differentiation suppression in osteoblasts via RIAM regulation of NF-κB nuclear translocation
Autor: | Shen Xm, Li Cc, Lan C, Lin Yf, Cheng L, Zhang Yz, Yan Sj |
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Rok vydání: | 2021 |
Předmět: | |
Zdroj: | Molecular and cellular endocrinology. 543 |
ISSN: | 1872-8057 |
Popis: | TLR4 is a key innate immune signal that mediates glucolipid toxicity through yet unclear mechanisms. Here, TLR4 truncation ameliorated bone metabolism disorders in diabetic rats, and the underlying mechanisms were explored by proteomics. Our study showed that TLR4 truncation inhibited bone loss induced by diabetes in rats. In addition, a proteomic analysis screen exposed the differential proteins associated with immune reactivity and T cell activation (RIAM and Class II histocompatibility antigen, M β1 chain). Further cellular experiments showed that TLR4 mediated the inhibition of osteoblast differentiation induced by glucolipotoxicity and promoted an increase in the nuclear level of RIAM-NF-κB. Mechanistic studies showed that TLR4 mediated glucolipotoxicity induced damage in bone metabolism primarily by regulating RIAM-NF-κB interactions, which promoted RIAM-NF-κB nuclear translocation. In conclusion, we confirmed that TLR4 inhibition could delay bone metabolism disorders induced by glycolipid toxicity via RIAM regulation of NF-κB nuclear translocation. |
Databáze: | OpenAIRE |
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