Fxyd5 activates the NFκB pathway and is involved in chondrocytes inflammation and extracellular matrix degradation.
Mol Med Rep
; 25(4)2022 Apr.
Article
em En
| MEDLINE
| ID: mdl-35191523
ABSTRACT
It is known that increased inflammation and extracellular matrix (ECM) degradation in chondrocytes can promote the development of osteoarthritis (OA). The FXYD domain containing ion transport regulator 5 (Fxyd5) has been found to promote chronic inflammatory responses. The present study aimed to investigate the role of Fxyd5 in OA. Murine ATDC5 chondrocytes were transfected with short hairpin RNAs specifically targeting Fxyd5 to silence its expression. Subsequently, cells were induced with lipopolysaccharide (LPS). The protein expression levels of Fxyd5, MMPs and proteins related to ECM, apoptosis and NFκB signaling were detected using western blot analysis. In addition, cell viability was assessed using a Cell Counting Kit8 assay, while the secretion of the proinflammatory factors and those of the oxidative stressrelated markers were measured using the corresponding kits. Finally, cells were treated with the NFκB activator, betulinic acid (BA) and the above experiments were repeated. The results demonstrated that Fxyd5 was significantly upregulated in ATDC5 cells treated with LPS. Additionally, Fxyd5 knockdown increased cell viability, enhanced the protein expression of Bcl2, Aggrecan and collagen II, while reduced the expression of Bax, cleaved caspase3/caspase3, MMP3 and MMP13 in LPSinduced ATDC5 cells. The production of IL1ß, IL6 and IL18 as well as reactive oxygen species and malondialdehyde, and the reduction of superoxide dismutase caused by LPS in ATDC5 cells, were also reversed by Fxyd5 silencing. Fxyd5 silencing inhibited the phosphorylation of p65 and IκBα induced by LPS. Finally, BA reversed the protective effect of Fxyd5 silencing on LPS induced chondrocytes injury. In conclusion, Fxyd5 could enhance chondrocyte inflammation and ECM degradation via activating the NFκB signaling.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Condrócitos
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2022
Tipo de documento:
Article