Investigating the Role of Circular RNAs Circ_0003972 and Circ-PTPN22 in Regulating Cytokine Expression in Postmenopausal Women with Osteoarthritis.

Background & Objective: Osteoarthritis (OA) is a common chronic inflammatory condition that gradually damages joints, leading to cartilage and joint tissue degeneration. It is associated with ongoing inflammation and an impaired immune system. Circular RNAs (circRNAs) and cytokines play key roles in regulating inflammation and joint tissue homeostasis in osteoarthritis. This study aims to assess the expression of circular RNAs (circular RNA-0003972 and circular RNA-PTPN22) and cytokines (IL-33, IL-36, IL-38, IL-40) in postmenopausal women with osteoarthritis compared with healthy controls, as potential new biomarkers for osteoarthritis. Methods: This study has a case-control design. Blood samples from 150 postmenopausal women (75 with newly diagnosed osteoarthritis and 75 healthy control subjects) were analyzed. Circular RNA 0003972, circular RNA-PTPN22, IL-33, IL-36, IL-38, and IL-40 were detected in peripheral blood from both groups using quantitative reverse transcription polymerase chain reaction (RT-qPCR), followed by bioinformatic analysis. Results: The levels of circular RNA 0003972 (p < 0.0001), circular RNA-PTPN22 (p < 0.001), and IL-40 (p < 0.0001) were significantly higher in the osteoarthritis group, while IL-38 was produced at lower levels in this group (p < 0.0001). Further, there was no significant difference in the expression of IL-33 and IL-36 between the cohorts. Of particular interest was the positive association between circular RNA-PTPN22 and IL-40 (r = 0.4, p < 0.001), suggesting a potential role in modulating the immune response. Conclusion: Our investigation found that patients with osteoarthritis had altered expression of specific circRNAs and cytokines (circular RNA 0003972, circular RNA-PTPN22, IL-38, and IL-40), which may serve as potential biomarkers and therapeutic targets, particularly in postmenopausal women. However, longitudinal investigations are required to determine whether these molecules can serve as effective biomarkers for diagnosis, prediction, and therapy monitoring.