Exploring the role of circ-0091579/miR-1225-5p and circ-HIPK3/miR-338-3p axes in the pathogenesis of postmenopausal osteoporosis.

CircRNAs have been increasingly appreciated as modulators of osteoporosis. This study investigated the expression of circ-0091579 and circ-HIPK3 in PBMCs of postmenopausal women with osteopenia and osteoporosis, aiming to underline their molecular mechanisms involved in pathogenesis of the disease. Seventy patients were stratified into two groups: 35 with osteopenia and 35 with osteoporosis, along with 30 healthy controls. Expressions of circ-0091579 and circ-HIPK3, miR-1225-5p and miR-338-3p, together with NF-κB, were assessed using RT-PCR. Keap1, Nrf2, and MAFB were determined using Western blot, while RANKL, OPG, IL-1β, and IL-6 were measured by ELISA. GSH and MDA were estimated colorimetrically. Data revealed that circ-0091579 was markedly upregulated, whereas miR-1225-5p was downregulated in patients relative to controls. Additionally, circ-HIPK3 was significantly decreased, while miR-338-3p was increased in the diseased groups. Circ-0091579 was directly correlated with RANKL/OPG, NF-κB, IL-1β, IL-6 and MDA, while inversely correlated with miR-1225-5p, T-score, BMD and GSH. Meanwhile, circ-HIPK3 and miR-338-3p were interrelated in an opposite manner. Eventually, the interplay among these downstream players induced an imbalance in bone homeostasis, triggering osteoporosis. Notably, these circRNAs differentiated patients from controls and those with osteopenia from osteoporotic ones. Thus, they could serve as biomarkers for early detection and tracking of osteoporosis.