miR-192-5p targets USP1 to regulate osteogenic differentiation and diagnose the occurrence of osteoporotic fracture

BACKGROUND: Osteoporosis (OP) in the elderly reduces bone strength, significantly increasing the risk of osteoporotic fracture (OPF). Early screening is essential to alleviate this widespread health problem, and miR-192-5p has recently been identified as a potential candidate. PURPOSE: To elucidate the diagnostic role of miR-192-5p in OPF patients and explore its underlying molecular mechanisms. METHODS: miR-192-5p expression in serum of OPF patients and hBMSCs was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The mRNA levels of osteogenic markers in hBMSCs were also quantified by RT-qPCR. The regulation of hBMSCs by miR-192-5p was determined through methyl thiazolyl tetrazolium (MTT) assay and flow cytometry. The downstream targets of miR-192-5p were validated through luciferase activity assay. The diagnostic potential of miR-192-5p for OPF was evaluated by receiver operating characteristic (ROC) method. RESULTS: miR-192-5p level was reduced in OPF patients, and its AUC for distinguishing OPF patients is 0.882. The levels of miR-192-5p and osteogenic markers runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN) and alkaline phosphatase (ALP) were upregulated after induction of differentiation in hBMSCs. Mechanically, inhibition of miR-192-5p may attenuate the upregulation of osteogenic markers and reduce the proliferation of hBMSCs by regulating ubiquitin specific peptidase 1 (USP1). CONCLUSION: miR-192-5p may serve as a potential biomarker for the diagnosis of OPF, and the miR-192-5p/USP1 axis offers a promising therapeutic target for OPF intervention.