MicroRNA-455-3p promotes osteoblast differentiation via targeting HDAC2

Background: Fragility fracture commonly occurs in the elderly, the basis of fracture healing is osteoblast regeneration. The study measured the expression changes of microRNA-455-3p during fracture healing in patients with fragility fractures, and explored its influence on osteoblast differentiation. Methods: 108 postmenopausal women with osteoporosis were recruited, in which 58 cases with fragility fracture. qRT-PCR was used for the measurement of miR-455-3p levels. MC3T3-E1 cells were induced differentiation by BMP-2. ELISA was performed for the measurement of alkaline phosphates (ALP), runtrelated transcription factor-2 (RUNX2), osteocalcin (OCN), and Collagen I. Luciferase reporter gene assay was done for the target gene analysis. Results: Serum miR-455-3p was significantly decreased in both osteoporosis and fragility fracture patients compared with the control group, which was most deficient in patients with fragility fracture. With the extension of treatment time, the level of miR-455-3p in serum increased gradually and reached the highest level at 4 weeks of treatment. Levels of miR-455-3p continued to increase on the 7th and 14th days after induction of cell differentiation. MiR-455-3p overexpression promoted cell proliferation, and increased the levels of osteoblast differentiation markers, including ALP, OCN, Collagen I, and RUNX2. MiR-455-3p in MC3T3-E1 cells was directly bound to HDAC2 and negatively regulated. Both MC3T3-E1 differentiation and the fracture healing of patients were accompanied by progressively reduced HDAC2. Conclusions: MiR-455-3p promotes osteogenic differentiation which may be associated with fracture healing, HDAC2 acts as a target of miR-455-3p in the underlying mechanism.(c) 2022 Elsevier Ltd. All rights reserved.