Circ_0128846/miR-140-3p/JAK2 Network in Osteoarthritis Development

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Circular RNAs (circRNAs) are key regulators of gene expression, influencing microRNA (miRNA) function, transcription, and splicing.
• Osteoarthritis (OA) is a degenerative joint disease with complex molecular underpinnings, necessitating the identification of novel therapeutic targets.

Purpose of the Study:

• To investigate the role of the novel circRNA, circ_0128846, in the progression of osteoarthritis (OA).
• To elucidate the molecular mechanism by which circ_0128846 influences OA pathogenesis, focusing on its interaction with miR-140-3p and JAK2.

Main Methods:

• Isolation of tissues and chondrocytes from OA patients and construction of experimental OA rat models.
• Overexpression and knockdown of circ_0128846 and JAK2 using cell transfection and siRNA interference.
• Quantitative real-time PCR (qRT-PCR), Western blot, dual-luciferase reporter assays, RNA immunoprecipitation (RIP), and immunohistochemistry (IHC) to assess gene expression and interactions.
• Hematoxylin and eosin (H&E) and Safranin O staining for pathological evaluation in animal models.

Main Results:

• Circ_0128846 and JAK2 were upregulated, while miR-140-3p was downregulated in OA patients.
• Circ_0128846 silencing enhanced chondrocyte viability, reduced apoptosis and inflammation, and suppressed MMP-13 while promoting collagen II expression by modulating the miR-140-3p/JAK2 axis.
• In vivo studies confirmed that circ_0128846 silencing attenuated OA progression and promoted collagen II expression.

Conclusions:

• Circ_0128846 acts as a sponge for miR-140-3p, increasing JAK2 expression and contributing to OA development.
• Targeting circ_0128846 demonstrates potential for alleviating OA progression, highlighting its significance as a therapeutic target.