Open AccessCircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758 ‐3p/ KDM6A axis
Author(s) -
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
Publication year - 2022
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13302
Subject(s) - chondrogenesis , cartilage , chondrocyte , microbiology and biotechnology , chemistry , osteoarthritis , aggrecan , downregulation and upregulation , microrna , homeostasis , biology , stem cell , anatomy , pathology , articular cartilage , biochemistry , medicine , gene , alternative medicine
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.