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Foxo3a aggravates inflammation and induces apoptosis in IL-1-treated rabbit chondrocytes via positively regulating tenascin-c
Affiliations- Department of Rehabilitation Medicine, The First People’s Hospital of Huzhou City, Huzhou City, Zhejiang Province, 313000, China
- Department of Nephrology, The First People’s Hospital of Huzhou City, Huzhou City, Zhejiang Province, 313000, China
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Abstract
Introduction. Osteoarthritis (OA) is the most common degenerative disease in middle-aged and elderly individuals that causes joint deformity and limb disability. Accumulating evidence has suggested that the pathogenesis of OA has been related to various mechanisms such as apoptosis, inflammation, oxidative stress and metabolic disorders. The aim of this study is to clarify the role of Foxo3a in the progress of OA in an in vitro model.
Materials and methods. The chondrocytes were derived from rabbit, and treated with IL-1β, which was used as an in vitro OA model. The over-expression and down-regulation of Foxo3a were achieved by transfection with overexpression vector or shRNA, respectively. The mRNA level of iNOS in chondrocytes was quantified by qPCR. Tenascin-c (Tnc) production was measured by ELISA and apoptosis-associated proteins were analyzed by Western blotting. The MTT assay was used to assess the viability of chondrocytes.
Results. Foxo3a and iNOS expression were upregulated in IL-1β-treated chondrocytes. Foxo3a silencing decreased iNOS expression, and inhibited apoptosis of IL-1β-treated chondrocytes. The production of Tnc was significantly increased in IL-1b-treated chondrocytes and was positively regulated by Foxo3. Importantly, extracellular addition of Tnc abrogated the protective effects of Foxo3a knockdown on IL-1β — treated chondrocytes.
Conclusion. The present study indicated that down-regulation of Foxo3a protected IL-1β-treated chondrocytes by decreasing iNOS expression and suppressing chondrocytes’ apoptosis via modulating tenascin-c, which could be regarded as a potent therapeutic target for the treatment of OA.
Abstract
Introduction. Osteoarthritis (OA) is the most common degenerative disease in middle-aged and elderly individuals that causes joint deformity and limb disability. Accumulating evidence has suggested that the pathogenesis of OA has been related to various mechanisms such as apoptosis, inflammation, oxidative stress and metabolic disorders. The aim of this study is to clarify the role of Foxo3a in the progress of OA in an in vitro model.
Materials and methods. The chondrocytes were derived from rabbit, and treated with IL-1β, which was used as an in vitro OA model. The over-expression and down-regulation of Foxo3a were achieved by transfection with overexpression vector or shRNA, respectively. The mRNA level of iNOS in chondrocytes was quantified by qPCR. Tenascin-c (Tnc) production was measured by ELISA and apoptosis-associated proteins were analyzed by Western blotting. The MTT assay was used to assess the viability of chondrocytes.
Results. Foxo3a and iNOS expression were upregulated in IL-1β-treated chondrocytes. Foxo3a silencing decreased iNOS expression, and inhibited apoptosis of IL-1β-treated chondrocytes. The production of Tnc was significantly increased in IL-1b-treated chondrocytes and was positively regulated by Foxo3. Importantly, extracellular addition of Tnc abrogated the protective effects of Foxo3a knockdown on IL-1β — treated chondrocytes.
Conclusion. The present study indicated that down-regulation of Foxo3a protected IL-1β-treated chondrocytes by decreasing iNOS expression and suppressing chondrocytes’ apoptosis via modulating tenascin-c, which could be regarded as a potent therapeutic target for the treatment of OA.
Keywords
chondrocytes; IL-1b; osteoarthritis in vitro; Foxo3a; iNOS; tenascin-c; apoptosis; shRNA
About this articleTitle
Foxo3a aggravates inflammation and induces apoptosis in IL-1-treated rabbit chondrocytes via positively regulating tenascin-c
Journal
Folia Histochemica et Cytobiologica
Issue
Article type
Original paper
Pages
1-8
Published online
2020-01-31
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1814
Article views/downloads
1353
DOI
Pubmed
Bibliographic record
Folia Histochem Cytobiol 2020;58(1):1-8.
Keywords
chondrocytes
IL-1b
osteoarthritis in vitro
Foxo3a
iNOS
tenascin-c
apoptosis
shRNA
Authors
Fei Wang
Qiubin Wang
Ming Zhu
Qi Sun
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