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Annals of agricultural and environmental medicine : AAEM · 2026

The function of miR-4666a-3p in the diagnosis of osteoporotic fractures and the promotion of fracture healing.

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Zou Xiangnan, Ren Zhongshu, Xu Haitao, Wang Hao

Аннотация

INTRODUCTION AND OBJECTIVE: MicroRNAs (miRNAs) regulate osteogenic differentiation in osteoporotic fractures (OF). The aim of the study is to investigate the diagnostic value and regulatory role of miR-4666a-3p in OF.

MATERIAL AND METHODS: The study is based on clinical samples (89 healthy controls, 79 OP patients, 83 OF patients) and hFOB1.19 cell experiments. RT-qPCR analyzed miR-4666a-3p expression, and logistic regression identified OF risk factors. ELISA measured RANKL and OPG concentrations. In vitro, osteoblast differentiation was induced to assess ALP activity, Runx2, Osteocalcin, Col1a1, cell viability (CCK-8), and apoptosis (flow cytometry). Target genes were bioinformatically predicted and confirmed via dual-luciferase assay. Rescue experiments explored the role of GSK3B in miR-4666a-3p-mediated osteogenic regulation. All experiments were repeated at least three times.

RESULTS: Downregulation of miR-4666a-3p could distinguish healthy controls and OP patients, further differentiate between OP and OF patients, and may predict the risk of OF occurrence. During osteoblast differentiation, miR-4666a-3p expression increased, ALP activity elevated, and key marker levels upregulated. Overexpression of miR-4666a-3p promoted osteoblast differentiation and activity, and reduced apoptosis rate, whereas inhibiting miR-4666a-3p had the opposite effect. MiR-4666a-3p negatively regulated the downstream target GSK3B. Overexpression of GSK3B reversed the osteogenic effects of miR-4666a-3p.

CONCLUSIONS: Downregulation of miR-4666a-3p may predict OF risk. Its upregulation promoted osteoblast differentiation by targeting GSK3B, potentially facilitating fracture healing.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты