title: miR-96 promotes osteogenic differentiation by suppressing HBEGF-EGFR signaling in osteoblastic cells.
abstract: MicroRNAs (miRNAs) are a class of small non-coding RNAs with important roles in various biological and pathological processes, including osteoblast differentiation. Here, we identified miR-96 as a positive regulator of osteogenic differentiation in a mouse osteoblastic cell line (MC3T3-E1) and in mouse bone marrow-derived mesenchymal stem cells. Moreover, we found that miR-96 down-regulates post-transcriptional expression of heparin-binding EGF-like growth factor (HB-EGF) by specifically binding to the 3'untranslated region of HB-EGF mRNA. Furthermore, in MC3T3-E1 cells, miR-96-induced HB-EGF down-regulation suppressed the phosphorylation of epidermal growth factor receptor (EGFR) and of extracellular signal-regulated kinase 1 (ERK1) and AKT, which both lie downstream of EGFR activation. Taken together, miR-96 promotes osteogenic differentiation by inhibiting HB-EGF and by blocking the HB-EGF-EGFR signaling pathway in osteoblastic cells.
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: bravepan@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Orthopaedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: happyzhou@vip.163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D035683:MicroRNAs; C541554:Mirn96 microRNA, mouse; D066246:ErbB Receptors
keywords: Differentiation; Heparin-binding epidermal growth factor-like growth factor; Osteogensis; miR-96