MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells.

摘要: Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional post-transcriptional mechanisms. Recently, microRNAs (miRNAs) were identified as novel key regulators of human stromal (skeletal, mesenchymal) stem cells (hMSC) differentiation. Here, we miRNA-34a (miR-34a) its target protein networks modulator osteoblastic (OB) hMSC. miRNA array profiling further validation quantitative RT-PCR revealed that miR-34a was upregulated during OB hMSC, in situ hybridization confirmed expression vivo. Overexpression inhibited early commitment late hMSC vitro, whereas inhibition anti-miR-34a enhanced these processes. Target prediction analysis experimental Jagged1 (JAG1), a ligand for Notch 1, bona fide miR-34a. siRNA-mediated reduction JAG1 Moreover, number known cell cycle regulator proliferation proteins, such cyclin D1, cyclin-dependent kinase 4 6 (CDK4 CDK6), E2F transcription factor three, division 25 homolog A among targets. Furthermore, preclinical model vivo formation, overexpression reduced heterotopic 60%, conversely, increased 200% miR-34a-deficient exhibited unique dual regulatory effects controlling both Tissue-specific might be potential therapeutic strategy enhancing formation.