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Updated: Jun 27, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Circ_QRICH1 promotes osteoarthritis progression by sponging miR-214-3p to impact ATF3-mediated chondrocyte
Shuanggen Yan1, Guangyu Li1, Yiliang Cui1
1Department of Orthopaedic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Objective:
To identify a circRNA with inhibitory activity towards chondrocyte ferroptosis which has therapeutic potential for osteoarthritis (OA).
Methods:
Whole transcriptome sequencing of joint cartilage tissues was performed in a rat model of OA and controls. circRNA and miRNA/mRNA targets were identified from a database search and verified by qPCR. The impact of the circRNA-miRNA-mRNA axis on mitochondrial function and ferroptosis was analyzed in in vivo and in vitro OA models.
Results:
The circ_QRICH1-miR-214-3p-ATF3 axis was differentially expressed in OA. AAV-sh-circ_QRICH1 treatment reduced pathological cartilage damage in OA rats, reduced ATF3 expression, increased miR-214-3p, Nrf2 and GPX4 expression in cartilage tissue, increased GSH and GSH-Px and reduced serum malondialdehyde (MDA). sh-circ_QRICH1 also reversed pathological damage and decreased Nrf2 and GPX4 caused by erastin treatment. circ_QRICH1, miR_214-3p and ATF3 were shown to interact in vitro and circ_QRICH1 knockdown restored mitochondrial function, reduced ferroptosis and improved the chondrocyte phenotype. Opposing effects were seen with circ_QRICH1 overexpression. Exogenous addition of miR-214-3p reversed the effects of circ_QRICH1 overexpression. ATF3 administration had similar effects to those of circ_QRICH1.
Conclusions:
A circ_QRICH1-miR-214-3p-ATF3 axis which targeted chondrocyte ferroptosis was identified and effects on osteoarthritis are described.
Insights
Researchers identified a novel circRNA, circ_QRICH1, that inhibits chondrocyte ferroptosis, offering therapeutic potential for osteoarthritis (OA). This discovery targets the circ_QRICH1-miR-214-3p-ATF3 axis, crucial for OA pathogenesis.
Area of Science:
- Molecular Biology
- Biochemistry
- Pathology
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown.
- Chondrocyte ferroptosis, a form of regulated cell death, plays a significant role in OA progression.
- Identifying novel molecular targets is crucial for developing effective OA therapies.
Purpose of the Study:
- To identify a specific circular RNA (circRNA) that can inhibit chondrocyte ferroptosis.
- To explore the therapeutic potential of this circRNA for treating osteoarthritis.
- To elucidate the molecular mechanism involving the circRNA, microRNA, and messenger RNA (mRNA) axis.
Main Methods:
- Whole transcriptome sequencing was performed on rat osteoarthritis cartilage tissues.
- circRNA, miRNA, and mRNA targets were identified and validated using qPCR.
- The impact of the identified circRNA-miRNA-mRNA axis on chondrocyte ferroptosis and mitochondrial function was analyzed in vitro and in vivo OA models.
Main Results:
- The circ_QRICH1-miR-214-3p-ATF3 axis was found to be differentially expressed in OA.
- Knockdown of circ_QRICH1 in OA rats reduced cartilage damage, decreased ATF3, and increased miR-214-3p, Nrf2, and GPX4 expression.
- circ_QRICH1 knockdown restored mitochondrial function and reduced ferroptosis in chondrocytes, improving their phenotype.
Conclusions:
- A novel circRNA, circ_QRICH1, targeting chondrocyte ferroptosis via the miR-214-3p-ATF3 axis was identified.
- This axis represents a potential therapeutic target for osteoarthritis.
- Modulating circ_QRICH1 shows promise for mitigating OA progression by inhibiting chondrocyte ferroptosis.
