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MiR-144-3p inhibits BMSC proliferation and osteogenic differentiation via targeting FZD4 in steroid-associated osteonecrosis.

BACKGROUND
MicroRNAs have recently been recognized to be involved in the development of bone diseases.


OBJECTIVE
The aim of this study was to investigate the effects of miR-144-3p on proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) from the patients with steroid-associated osteonecrosis (ONFH) and its underlying mechanism.


METHOD
The expression of miR-144-3p in the MSCs from the proximal femur of 10 patients with ONFH and 10 patients with femoral neck fractures was examined by Real-time PCR. The cell proliferation assay was performed by MTT. The osteogenic differentiation of MSCs was assayed by Alizarin Red S (ARS) staining. And the interaction between miR-144-3p and FZD4 was investigated by western blot, Real-time PCR and luciferase reporter assay.


RESULTS
ONFH samples had the obviously high expression of miR-144-3p compared to the control. MiR-144-3p exerted an inhibitory effect on the proliferation and osteogenic differentiation of MSCs. By targeting FZD4, miR-144-3p decreased nuclear translocation of β-catenin, the transcription of RUNX2 and COL1A1. Over-expression of FZD4 partially reversed miR-144-3p-induced decrease in the proliferation and osteogenic differentiation of MSCs.


CONCLUSION
MiR-144-3p might act an important role in the development of ONFH and could be used as a novel class of therapeutic targets for this disease.