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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...

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Autores principales: 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
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
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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.
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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
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