open access

Vol 58, No 1 (2020)
Original paper
Submitted: 2019-07-16
Accepted: 2019-12-30
Published online: 2020-01-31
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Foxo3a aggravates inflammation and induces apoptosis in IL-1-treated rabbit chondrocytes via positively regulating tenascin-c

Fei Wang1, Qiubin Wang1, Ming Zhu2, Qi Sun1
DOI: 10.5603/FHC.a2019.0022
·
Pubmed: 32003441
·
Folia Histochem Cytobiol 2020;58(1):1-8.
Affiliations
  1. Department of Rehabilitation Medicine, The First People’s Hospital of Huzhou City, Huzhou City, Zhejiang Province, 313000, China
  2. Department of Nephrology, The First People’s Hospital of Huzhou City, Huzhou City, Zhejiang Province, 313000, China

open access

Vol 58, No 1 (2020)
ORIGINAL PAPERS
Submitted: 2019-07-16
Accepted: 2019-12-30
Published online: 2020-01-31

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.

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Keywords

chondrocytes; IL-1b; osteoarthritis in vitro; Foxo3a; iNOS; tenascin-c; apoptosis; shRNA

About this article
Title

Foxo3a aggravates inflammation and induces apoptosis in IL-1-treated rabbit chondrocytes via positively regulating tenascin-c

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 58, No 1 (2020)

Article type

Original paper

Pages

1-8

Published online

2020-01-31

DOI

10.5603/FHC.a2019.0022

Pubmed

32003441

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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