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

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.

To elucidate the diagnostic role of miR-192-5p in OPF patients and explore its underlying molecular mechanisms.

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.

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).

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.