Published January 4, 2010 - More info
MicroRNAs (miRNAs) interfere with translation of specific target mRNAs and are thought to thereby regulate many cellular processes. Recent studies have suggested that miRNAs might play a role in osteoblast differentiation and bone formation. Here, we identify a new miRNA (miR-2861) in primary mouse osteoblasts that promotes osteoblast differentiation by repressing histone deacetylase 5 (HDAC5) expression at the post-transcriptional level. miR-2861 was found to be transcribed in ST2 stromal cells during bone morphogenetic protein 2–induced (BMP2-induced) osteogenesis, and overexpression of miR-2861 enhanced BMP2-induced osteoblastogenesis, whereas inhibition of miR-2861 expression attenuated it. HDAC5, an enhancer of runt-related transcription factor 2 (Runx2) degradation, was confirmed to be a target of miR-2861. In vivo silencing of miR-2861 in mice reduced Runx2 protein expression, inhibited bone formation, and decreased bone mass. Importantly, miR-2861 was found to be conserved in humans, and a homozygous mutation in pre–miR-2861 that blocked expression of miR-2861 was shown to cause primary osteoporosis in 2 related adolescents. Consistent with the mouse data, HDAC5 levels were increased and Runx2 levels decreased in bone samples from the 2 affected individuals. Thus, our studies show that miR-2861 plays an important physiological role in osteoblast differentiation and contributes to osteoporosis via its effect on osteoblasts.
Hui Li, Hui Xie, Wei Liu, Rong Hu, Bi Huang, Yan-Fei Tan, Er-Yuan Liao, Kang Xu, Zhi-Feng Sheng, Hou-De Zhou, Xian-Ping Wu, Xiang-Hang Luo
Original citation: J. Clin. Invest.119:3666–3677 (2009). doi:10.1172/JCI39832.
Citation for this corrigendum: J. Clin. Invest.120:395 (2010). do:10.1172/JCI39832C1.
Er-Yuan Liao has chosen to remove his name from the list of authors, as his contribution merited acknowledgment only. The corrected author list appears above.
In Figure 5A, the second and third bars were inadvertently mislabeled. The correct Figure 5A appears below.
In Figure 8B, the third panel was a duplicate of the third panel in Figure 8C and should not have appeared. The correct Figure 8B appears below.
The authors and the JCI regret the errors.