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Updated: Sep 5, 2025

Visualization of Chondrocyte Intercalation and Directional Proliferation via Zebrabow Clonal Cell Analysis in the Embryonic Meckel’s Cartilage
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CircNFIX regulates chondrogenesis and cartilage homeostasis by targeting the miR758-3p/KDM6A axis

Hongyi Liao1,2, Qingqiang Tu1,2, Yunze Kang1,2

  • 1Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Cell Proliferation
|July 6, 2022
PubMed
Abstract

Insights

Circular RNAs (circRNAs) like circNFIX are crucial for cartilage health and osteoarthritis (OA) development. This study shows circNFIX protects against chondrocyte degradation and OA progression, offering a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Osteoarthritis (OA) involves progressive articular cartilage destruction with unclear etiology.
  • Circular RNAs (circRNAs) are implicated in cartilage degeneration and OA pathogenesis.
  • circNFIX has emerged as a potential regulator of chondrogenesis and cartilage homeostasis.

Purpose of the Study:

  • To investigate the role of circNFIX in chondrogenesis and cartilage homeostasis.
  • To elucidate the molecular mechanisms underlying circNFIX's function in osteoarthritis.
  • To assess circNFIX as a potential therapeutic target for OA.

Main Methods:

  • Microarray analysis of circRNA expression during human adipose-derived stem cell (hADSC) chondrogenesis.
  • Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization for circNFIX detection.
  • Gain- and loss-of-function studies, RNA pull-down, Argonaute2-RNA immunoprecipitation (Ago2-IP), and luciferase reporter assays to determine molecular interactions.

Main Results:

  • CircNFIX expression dynamics observed during hADSC chondrogenesis (upregulated early/mid-stage, downregulated late-stage).
  • CircNFIX inhibition impaired hADSC chondrogenesis; circNFIX overexpression protected chondrocytes and alleviated OA progression in vivo.
  • Mechanistically, circNFIX functions as a sponge for miR-758-3p, regulating the miR-758-3p/KDM6A axis.

Conclusions:

  • CircNFIX plays a critical role in regulating chondrogenesis and maintaining cartilage homeostasis.
  • Dysregulation of circNFIX is associated with osteoarthritis development and progression.
  • CircNFIX represents a promising therapeutic target for osteoarthritis treatment.

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