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Hsa_circular RNA_0045474 Facilitates Osteoarthritis Via Modulating microRNA-485-3p and Augmenting Transcription Factor 4

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Abstract

Circular RNA (circRNA) influences on the pathological process of osteoarthritis (OA) and may be a potential marker for disease diagnosis. The study was to scrutinize the association of circ_0045474 with OA. Clinical samples of OA patients were collected, and 12 circRNAs derived from KPNA2 gene were examined. CHON-001 cells were stimulated with IL-1β to construct an OA chondrocyte model. miR-485-3p, transcription factor 4 (TCF4) and circ_0045474, type II procollagen (COL2A1), and human collagenase-3 (MMP13) were tested. Furthermore, cell activities were analyzed. The relationship between miR-485-3p, TCF4, and circ_0045474 was determined. The role of circ_0045474 in vivo was further confirmed by constructing an OA mouse model by anterior cruciate ligament transection. circ_0045474 expression was elevated in OA patients. Suppressing circ_0045474 restrained IL-1β-stimulated extracellular matrix degradation, inflammatory cytokine secretion, and chondrocyte apoptosis. Circ_0045474 competitively combined with miR-485-3p, while TCF4 was the target of miR-485-3p. Circ_0045474 modulated IL-1β-stimulated extracellular matrix degradation, inflammatory cytokine secretion, and chondrocyte apoptosis via miR-485-3p/TCF4 axis. Suppressing circ 0045474 was effective to alleviate OA in mice. Silenced circ_0045474 suppresses OA progression in vitro and vivo via miR-485-3p/TCF4 axis. In short, circ_0045474 can be considered a novel therapeutic target for OA.

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Data Availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Author notes

  1. ZhenXing Zhang and PingHua Yu are co-first authors and contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics II, Haining People’s Hospital, Haining, 314400, Zhejiang, China

    ZhenXing Zhang

  2. Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China

    PingHua Yu

  3. Trauma Center, The Second People’s Hospital of Lianyungang, No.41, Hailian East Road, Xinpu District, Lianyungang, 222002, Jiangsu, China

    LinGang Bai

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  1. ZhenXing Zhang
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Correspondence to LinGang Bai.

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Ethical Approval

The present study was approved by the Ethics Committee of Haining People’s Hospital and written informed consent was provided by all patients prior to the study start. All procedures were performed in accordance with the ethical standards of the Institutional Review Board and The Declaration of Helsinki, and its later amendments or comparable ethical standards (Approval number: 201806HN01). And the experiments were approved by the Institutional Animal Care and Use Committee of Haining People’s Hospital and all procedures complied with the National Institutes of Health Guide for the Use of Laboratory Animals (Approval number: 201806HN20).

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Zhang, Z., Yu, P. & Bai, L. Hsa_circular RNA_0045474 Facilitates Osteoarthritis Via Modulating microRNA-485-3p and Augmenting Transcription Factor 4. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-023-01019-z

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