MiR-488 promotes fracture healing by targeting DKK1

F. Wang, X.-Y. Hu, C. Cao, Y.-W. Zhao, S.-H. He

Department of Traumatic Orthopaedics, The First People’s Hospital of Changzhou, Changzhou, China. biggestbee@163.com

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• Pharmacology

OBJECTIVE: The aim of this study was to evaluate the effect of miR-488 on fracture healing and to investigate the possible underlying mechanism.

PATIENTS AND METHODS: The expression level of miR-488 in clinical cases was detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). After prediction of the potential target of miR-488 in websites, three groups were established to elucidate the effects of miR-488 and Dickkopf1 (DKK1) on osteoblasts function: the miR-NC group (negative control), the miR-488 mimics group (MC3T3-E1 cells transfected with miR-488 mimics) and the mimics + si-DKK1 group (MC3T3-E1 cells transfected with miR-488 mimics and si-DKK1). Subsequently, cell viability, apoptosis rate of osteoblasts and osteogenesis-associated markers were determined respectively.

RESULTS: In the present study, we found that the expression of miR-488 in patients with osteoporosis was significantly lower than that of healthy controls. The potential target of miR-488 was predicted by three public databases. Luciferase reporter gene assay confirmed that DKK1 was a direct target of miR-488. Besides, the overexpression of miR-488 could significantly reduce the transcription and translation levels of DKK1. These results suggested that miR-488 had a negative regulatory effect on DKK1. Subsequent experiments demonstrated that decreased expression of DKK1 induced by miR-488 up-regulation could significantly improve cell viability and suppress cell apoptosis. Meanwhile, the expression levels of osteogenesis-associated markers were remarkably elevated.

CONCLUSIONS: Our research revealed the role of miR-488 in promoting osteoblast function. This indicated that miR-488 could be a potential therapeutic target for fracture healing.

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