Overexpression of miR-671-3p alleviates postmenopausal osteoporosis by targeting GREM2 to activate BMP2/SMAD signaling pathway.

Abstract

Background: Increased fracture risk is linked to postmenopausal osteoporosis (PMOP), and elucidating the function of microRNAs (miRNAs) in this condition is vital for identifying individuals at high risk of fractures. This research focused on exploring the function and mechanism of miR-671-3p in PMOP.

Methods: Using qRT-PCR, we measured the expression levels of miR-671-3p in the serum of PMOP patients and evaluated its predictive capacity for osteoporosis occurrence through Receiver Operating Characteristic (ROC) analysis. An in vitro model of MC3T3-E1 osteoblasts cultured under simulated microgravity (MG) was established to mimic the osteoporosis-related bone loss microenvironment. It was used to investigate miR-671-3p's regulatory effects on cell proliferation (CCK-8 assay), apoptosis (Annexin V/PI staining), and osteogenic differentiation (ALP activity and osteogenic marker mRNA levels). Dual luciferase reporter gene assays and RNA immunoprecipitation (RIP) experiments were performed to validate the interaction between miR-671-3p and GREM2.

Results: miR-671-3p expression was reduced in PMOP patients and in MG-exposed MC3T3-E1 cells. miR-671-3p exhibited strong predictive power for early detection of PMOP. When miR-671-3p was overexpressed, it enhanced osteogenic differentiation and suppressed apoptosis in MC3T3-E1 cells. GREM2 was pinpointed as a target of miR-671-3p, which inhibited osteogenic differentiation in MC3T3-E1 cells and accelerated MG-induced apoptosis. By inhibiting GREM2 expression, overexpression of miR-671-3p activated the BMP2/SMAD signaling pathway.

Conclusion: Reduced miR-671-3p expression may signal the presence of PMOP. By targeting GREM2 to activate the BMP2/SMAD pathway, miR-671-3p may stimulate osteogenic differentiation, foster bone formation, and prevent the onset of osteoporosis.