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Serum miR-576-5p as a novel diagnostic biomarker and therapeutic target for osteoarthritis via targeting
Mengye Weng1, Zhigang Yang1, Xiaoying Feng2
1Department of Orthopedics, Affiliated Hospital of Jiangnan University, Wuxi City, Jiangsu Province, China.
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.
Insights
Osteoarthritis patients have lower miR-576-5p levels, a potential diagnostic biomarker. This microRNA alleviates osteoarthritis by targeting KLF10, reducing chondrocyte dysfunction and inflammation.
Area of Science:
- Biochemistry
- Molecular Biology
- Biomarkers
Background:
- Osteoarthritis (OA) is a degenerative joint disease with progressive cartilage breakdown, lacking effective biomarkers and disease-modifying therapies.
- Dysregulated microRNAs (miRNAs) are implicated in OA pathogenesis.
- This study investigates the diagnostic potential and functional role of miR-576-5p in OA.
Purpose of the Study:
- To explore miR-576-5p as a diagnostic biomarker for Osteoarthritis (OA).
- To elucidate the functional mechanism of miR-576-5p in OA pathogenesis.
- To investigate the therapeutic potential of miR-576-5p in OA.
Main Methods:
- Serum miR-576-5p levels were quantified in OA patients and healthy controls (HC) via qRT-PCR.
- Diagnostic performance was evaluated using Receiver Operating Characteristic (ROC) analysis.
- In vitro chondrocyte injury models and bioinformatic analyses identified KLF10 as a target of miR-576-5p.
Main Results:
- OA patients showed significantly lower serum miR-576-5p levels compared to HC (AUC=0.886).
- Downregulation of miR-576-5p in chondrocytes increased apoptosis and inflammation, effects reversed by miR-576-5p restoration.
- KLF10 was validated as a direct target, with its overexpression counteracting miR-576-5p's protective effects.
Conclusions:
- miR-576-5p is a promising diagnostic biomarker for OA.
- miR-576-5p alleviates OA progression by targeting KLF10, reducing chondrocyte dysfunction.
- These findings suggest novel miRNA-based therapeutic strategies for OA.
