Cargando…
CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis
OBJECTIVES: Osteoarthritis (OA) is a degenerative disease causing the progressive destruction of articular cartilage; however, the aetiology has not yet been elucidated. Circular RNAs (circRNAs) are reportedly involved in cartilage degeneration and OA development. In the present study, we identified...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628241/ https://www.ncbi.nlm.nih.gov/pubmed/35791460 http://dx.doi.org/10.1111/cpr.13302 |
_version_ | 1784823154359664640 |
---|---|
author | Liao, Hongyi Tu, Qingqiang Kang, Yunze Mao, Guping Li, Zhiwen Hu, Shu Sheng, Puyi Wang, Xudong Xu, Yiyang Long, Dianbo Xu, Yuanyuan Kang, Yan Zhang, Ziji |
author_facet | Liao, Hongyi Tu, Qingqiang Kang, Yunze Mao, Guping Li, Zhiwen Hu, Shu Sheng, Puyi Wang, Xudong Xu, Yiyang Long, Dianbo Xu, Yuanyuan Kang, Yan Zhang, Ziji |
author_sort | Liao, Hongyi |
collection | PubMed |
description | OBJECTIVES: Osteoarthritis (OA) is a degenerative disease causing the progressive destruction of articular cartilage; however, the aetiology has not yet been elucidated. Circular RNAs (circRNAs) are reportedly involved in cartilage degeneration and OA development. In the present study, we identified that circNFIX regulates chondrogenesis and cartilage homeostasis. MATERIALS AND METHODS: Microarray analysis was performed to explore circRNA expression during the chondrogenic differentiation of human adipose‐drived stem cells (hADSCs). CircNFIX expression was determined using quantitative reverse transcription‐polymerase chain reaction and in situ hybridization. Gain‐ and loss‐of‐function assays were performed to validate the role of circNFIX in cartilage homeostasis. RNA pull‐down, Argonaute2‐RNA immunoprecipitation and luciferase reporter assays were performed to evaluate the interactions among circNFIX, miR758‐3p and KDM6A. RESULTS: CircNFIX expression was upregulated in the early and middle stages, whereas downregulated in the late stage of hADSC chondrogenesis. CircNFIX inhibition attenuated hADSC chondrogenesis. CircNFIX was remarkably downregulated in OA samples, circNFIX overexpression protected against chondrocyte degradation and alleviated OA progression in the destabilization of the medial meniscus OA model. Mechanistically, circNFIX acted as a sponge of miR758‐3p and played a role in the chondrogenesis and chondrocyte degeneration by targeting the miR‐758‐3p/KDM6A axis. CONCLUSIONS: Our results revealed a key role of circNFIX in chondrogenesis and cartilage homeostasis, which may provide a potential therapeutic strategy for OA treatment. |
format | Online Article Text |
id | pubmed-9628241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96282412022-11-03 CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis Liao, Hongyi Tu, Qingqiang Kang, Yunze Mao, Guping Li, Zhiwen Hu, Shu Sheng, Puyi Wang, Xudong Xu, Yiyang Long, Dianbo Xu, Yuanyuan Kang, Yan Zhang, Ziji Cell Prolif Original Articles OBJECTIVES: Osteoarthritis (OA) is a degenerative disease causing the progressive destruction of articular cartilage; however, the aetiology has not yet been elucidated. Circular RNAs (circRNAs) are reportedly involved in cartilage degeneration and OA development. In the present study, we identified that circNFIX regulates chondrogenesis and cartilage homeostasis. MATERIALS AND METHODS: Microarray analysis was performed to explore circRNA expression during the chondrogenic differentiation of human adipose‐drived stem cells (hADSCs). CircNFIX expression was determined using quantitative reverse transcription‐polymerase chain reaction and in situ hybridization. Gain‐ and loss‐of‐function assays were performed to validate the role of circNFIX in cartilage homeostasis. RNA pull‐down, Argonaute2‐RNA immunoprecipitation and luciferase reporter assays were performed to evaluate the interactions among circNFIX, miR758‐3p and KDM6A. RESULTS: CircNFIX expression was upregulated in the early and middle stages, whereas downregulated in the late stage of hADSC chondrogenesis. CircNFIX inhibition attenuated hADSC chondrogenesis. CircNFIX was remarkably downregulated in OA samples, circNFIX overexpression protected against chondrocyte degradation and alleviated OA progression in the destabilization of the medial meniscus OA model. Mechanistically, circNFIX acted as a sponge of miR758‐3p and played a role in the chondrogenesis and chondrocyte degeneration by targeting the miR‐758‐3p/KDM6A axis. CONCLUSIONS: Our results revealed a key role of circNFIX in chondrogenesis and cartilage homeostasis, which may provide a potential therapeutic strategy for OA treatment. John Wiley and Sons Inc. 2022-07-05 /pmc/articles/PMC9628241/ /pubmed/35791460 http://dx.doi.org/10.1111/cpr.13302 Text en © 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Liao, Hongyi Tu, Qingqiang Kang, Yunze Mao, Guping Li, Zhiwen Hu, Shu Sheng, Puyi Wang, Xudong Xu, Yiyang Long, Dianbo Xu, Yuanyuan Kang, Yan Zhang, Ziji CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis |
title |
CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis |
title_full |
CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis |
title_fullStr |
CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis |
title_full_unstemmed |
CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis |
title_short |
CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758‐3p/KDM6A axis |
title_sort | circnfix regulates chondrogenesis and cartilage homeostasis by targeting the mir758‐3p/kdm6a axis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628241/ https://www.ncbi.nlm.nih.gov/pubmed/35791460 http://dx.doi.org/10.1111/cpr.13302 |
work_keys_str_mv | AT liaohongyi circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT tuqingqiang circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT kangyunze circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT maoguping circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT lizhiwen circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT hushu circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT shengpuyi circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT wangxudong circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT xuyiyang circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT longdianbo circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT xuyuanyuan circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT kangyan circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis AT zhangziji circnfixregulateschondrogenesisandcartilagehomeostasisbytargetingthemir7583pkdm6aaxis |