A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans

• DOI: 10.1172/jci39832
• Publication Date: 2009-11-30T19:52:33Z
• Authors: 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
• Keywords: RUNX2; Histone deacetylase 5

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 bone formation. Here, we identify new miRNA (miR-2861) primary mouse osteoblasts promotes by repressing histone deacetylase 5 (HDAC5) expression at the post-transcriptional level. miR-2861 was found be transcribed ST2 stromal cells during morphogenetic protein 2-induced (BMP2-induced) osteogenesis, overexpression enhanced BMP2-induced osteoblastogenesis, whereas inhibition attenuated it. HDAC5, an enhancer runt-related transcription factor 2 (Runx2) degradation, confirmed miR-2861. In vivo silencing mice reduced Runx2 expression, inhibited formation, decreased mass. Importantly, conserved humans, homozygous mutation pre-miR-2861 blocked shown cause osteoporosis related adolescents. Consistent data, HDAC5 levels were increased samples from affected individuals. Thus, our show plays important physiological contributes via its effect on osteoblasts.