Osteoporosis is a common disease that can seriously impair the physical and mental health of the elderly. However, current treatment is unsatisfactory, due to the lack of effective therapeutic targets. Abnormal expression and involvement of microRNA-142 (miR-142) have been identified in many diseases, including bone-related diseases. Herein, we explored the effect of miR-142 on the viability, differentiation and apoptosis of the mouse pre-osteoblast cell line MC3T3-E1. We observed that the viability of MC3T3-E1 cells was significantly inhibited or promoted after transfection of miR-142 mimic or inhibitor, respectively. The apoptotic rate was dramatically increased by miR-142 mimic and decreased by inhibitor compared with the negative control (NC) group. Bcl-2 expression was down-regulated in the miR-142 mimic group and up-regulated in the miR-142 inhibitor group, whilst levels of cleaved Caspase 3 and Bax were increased in the miR-142 mimic group and reduced in the miR-142 inhibitor group. Expression changes of Runx2 and Osteocalcin (OCN) suggest that miR-142 inhibits the differentiation of osteoblast cells. Moreover, the luciferase reporter assay was used to verify that bone morphogenetic protein 2 (BMP2) is a target of miR-142. Overexpression of BMP2 repressed the pro-apoptotic effect of miR-142 mimic whilst knockdown of BMP2 abolished the inhibitory effect of miR-142 inhibitor on the apoptosis of MC3T3-E1 cells. Furthermore, up or down-regulation of miR-142 dramatically decreased or increased the ratio of p-Smad1/5/Smad1 as well as p-Smad1/5/Smad5, respectively. Collectively, our results imply that miR-142 might influence the viability and differentiation of osteoblast cells by regulating BMP2 and BMP/Smad signaling.This article is protected by copyright. All rights reserved.