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Background <p>Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, and currently lacks effective biomarkers and disease-modifying therapies. Dysregulated microRNAs (miRNAs) have been implicated in OA pathogenesis. This study explores the diagnostic potential and functional mechanism of miR-576-5p in OA.</p> Methods <p>Serum levels of miR-576-5p were measured in 61 OA patients and 60 healthy controls (HC) using qRT-PCR. Diagnostic performance was assessed using ROC analysis. An in vitro model of chondrocyte injury was established by treating the human chondrocyte cell line C-28/I2 with IL-1β. The effects of miR-576-5p on cell viability, apoptosis, and inflammatory response were evaluated. Bioinformatic predictions and dual-luciferase reporter assays were used to identify Krüppel-like factor 10 (KLF10) as a target of miR-576-5p. Rescue experiments were conducted to confirm the functional interaction between miR-576-5p and KLF10.</p> Results <p>OA patients exhibited significantly lower serum miR-576-5p levels than HC, with an AUC of 0.886. Low miR-576-5p expression correlated with higher KL grades, WOMAC/VAS scores, and elevated CRP/CTX-II/COMP levels. In IL-1β-stimulated chondrocytes, miR-576-5p was downregulated, leading to decreased viability, increased apoptosis, and elevated IL-6/IL-8/TNF-α secretion. These effects were reversed by miR-576-5p overexpression. KLF10 was confirmed as a direct target, showing inverse correlation with miR-576-5p. Overexpression of KLF10 counteracted the protective effects of miR-576-5p, reinstating inflammatory response and apoptosis.</p> Conclusions <p>miR-576-5p represents a promising diagnostic biomarker for OA and alleviates disease progression by targeting KLF10, thereby reducing chondrocyte dysfunction. These results offer new insights into miRNA-based therapeutics for OA.</p>

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Serum miR-576-5p as a novel diagnostic biomarker and therapeutic target for osteoarthritis via targeting KLF10-mediated chondrocyte dysfunction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月9日

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  • Mengye Weng,
  • Zhigang Yang,
  • Xiaoying Feng

摘要

Background

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, and currently lacks effective biomarkers and disease-modifying therapies. Dysregulated microRNAs (miRNAs) have been implicated in OA pathogenesis. This study explores the diagnostic potential and functional mechanism of miR-576-5p in OA.

Methods

Serum levels of miR-576-5p were measured in 61 OA patients and 60 healthy controls (HC) using qRT-PCR. Diagnostic performance was assessed using ROC analysis. An in vitro model of chondrocyte injury was established by treating the human chondrocyte cell line C-28/I2 with IL-1β. The effects of miR-576-5p on cell viability, apoptosis, and inflammatory response were evaluated. Bioinformatic predictions and dual-luciferase reporter assays were used to identify Krüppel-like factor 10 (KLF10) as a target of miR-576-5p. Rescue experiments were conducted to confirm the functional interaction between miR-576-5p and KLF10.

Results

OA patients exhibited significantly lower serum miR-576-5p levels than HC, with an AUC of 0.886. Low miR-576-5p expression correlated with higher KL grades, WOMAC/VAS scores, and elevated CRP/CTX-II/COMP levels. In IL-1β-stimulated chondrocytes, miR-576-5p was downregulated, leading to decreased viability, increased apoptosis, and elevated IL-6/IL-8/TNF-α secretion. These effects were reversed by miR-576-5p overexpression. KLF10 was confirmed as a direct target, showing inverse correlation with miR-576-5p. Overexpression of KLF10 counteracted the protective effects of miR-576-5p, reinstating inflammatory response and apoptosis.

Conclusions

miR-576-5p represents a promising diagnostic biomarker for OA and alleviates disease progression by targeting KLF10, thereby reducing chondrocyte dysfunction. These results offer new insights into miRNA-based therapeutics for OA.