miR-1236 regulates osteogenic and adipogenic differentiation by targeting BMP3 in osteoporotic fracture

Osteoporotic fracture (OPF) has become a major global public health issue. We aim to investigate the serum expression and fracture risk association of miR-1236 in OPF and its mechanisms in bone metabolism.

This study included 83 osteoporosis (OP) patients and 93 OPF patients. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze gene expression levels. Lipofectamine 2000 was used to overexpress or inhibit miR-1236 in hFOB 1.19 human osteoblast cells and human bone marrow-derived mesenchymal stem cells (hBMSCs). Osteogenic differentiation was induced in hFOB 1.19 cells and adipogenic differentiation in hBMSCs. BMP3 was predicted as a target of miR-1236 by TargetScan and validated by dual-luciferase reporter assay. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to assess cell proliferation and apoptosis.

Serum miR-1236 was down-regulated in OPF patients. OPF patients presented elevated serum bone-metabolic markers (β-CTX, P1NP and BMP-3). miR-1236 was correlated with these bone-related markers in OPF patients. In hFOB 1.19 cells, miR-1236 promoted osteogenic differentiation. BMP3 was negatively regulated by miR-1236 and exerted an inhibitory effect on osteogenic differentiation. In hBMSCs, miR-1236 suppressed adipogenic differentiation, whereas BMP3 promoted adipogenic differentiation.

Serum miR-1236 is decreased in patients with OPF, and is correlated with altered bone-metabolic markers. In-vitro findings demonstrate that miR-1236 promotes osteogenic differentiation and inhibits adipogenic differentiation by targeting BMP3.