Circular RNA PVT1 promotes osteoarthritis progression through the miR-550a-3p/CX3CR1 pathway: A mechanistic study

Circular RNAs (circRNAs) are increasingly recognized as pivotal factors in the pathogenesis of osteoarthritis (OA). CircPVT1 (ID has_circ_0001821), a circRNA family member, plays a substantial role in the progression of various human diseases; however, its specific function in OA remains to be clarified. This study aims to elucidate the expression patterns and interactions among circPVT1, miR-550a-3p, and CX3CR1 in OA, to establish a circPVT1-miR-550a-3p-CX3CR1 competitive endogenous RNA (ceRNA) network, and to evaluate its role in OA chondrocytes and its potential clinical implications.

First, a ceRNA network involving circPVT1, miR-550a-3p, and CX3CR1 was constructed using bioinformatics tools. Subsequently, direct targeting relationships between circPVT1 and miR-550a-3p, as well as between miR-550a-3p and CX3CR1, were confirmed through dual-luciferase reporter assays. Lastly, the expression patterns and interactions of circPVT1, miR-550a-3p, and CX3CR1 in OA chondrocytes, as well as their impact on chondrocyte proliferation, apoptosis, inflammatory responses, and extracellular matrix regulation, were studied using techniques such as real-time quantitative PCR, Western blot, CCK-8 cell proliferation assay, flow cytometry, and ELISA.

The results indicate that circPVT1 is abnormally upregulated in OA chondrocytes. The aberrant expression of circPVT1 impacts chondrocyte proliferation, apoptosis, inflammatory responses, and the synthesis and degradation of the extracellular matrix. Moreover, circPVT1 upregulates CX3CR1 expression by inhibiting miR-550a-3p, thereby affecting the pathological state of OA chondrocytes.

Elevated expression of circPVT1 in OA chondrocytes indicates a poor prognosis for OA patients. CircPVT1 acts as a ceRNA, competing with miR-550a-3p and weakening its inhibition of CX3CR1, thus boosting CX3CR1 levels, subsequently affecting chondrocyte growth and cell death, the release of inflammatory mediators, and both the formation and breakdown of the extracellular matrix. These findings suggest that circPVT1 could be an important biomarker and therapeutic target for OA.