title: U0126 promotes osteogenesis of rat bone-marrow-derived mesenchymal stem cells by activating BMP/Smad signaling pathway.
abstract: U0126 has been reported as a specific inhibitor of the ERK1/2 signaling pathway, which plays a vital role during the osteogenic differentiation of mesenchymal stem cells (MSCs). We report the positive effect of U0126 on the osteogenesis of rat MSCs. We find that U0126 promotes the osteogenic differentiation of rat MSCs as demonstrated by the quantitative real-time polymerase chain reaction for osteogenic markers, alkaline phosphatase activity and calcium nodule formation. Our data indicate that U0126 enhances the BMP/Smad signaling pathway in rat MSCs, while inhibiting the ERK1/2 signaling pathway. Furthermore, Western blot results demonstrate that U0126 increases Smad1/5/8 phosphorylation synergistically with β-glycerophosphate. In addition, U0126 significantly increases the expression of BMP2 during the process of osteogenesis in rat MSCs and the level of phosphorylated Smad1/5/8 is significantly reduced by BMP2 antibody, suggesting that U0126 also promotes the expression of BMP2 to enhance Smad proteins phosphorylation. Thus, we demonstrate a novel function for U0126 in promoting osteogenic differentiation of rat MSCs by the activation of the BMP/Smad signaling pathway.
authors.affiliation: Department of Orthopaedics & Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics & Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Orthopaedics & Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Kuixing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics & Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Wong
authors.affiliation: Department of Orthopaedics & Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Sien
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Orthopaedics & Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People's Republic of China. gangli@cuhk.edu.hk.|MOE Key Laboratory of Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, People's Republic of China. gangli@cuhk.edu.hk.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China. gangli@cuhk.edu.hk.|Li Ka Shing Institute of Health Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong, SAR, People's Republic of China. gangli@cuhk.edu.hk.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D002070:Butadienes; D005994:Glycerophosphates; D009570:Nitriles; D051785:Smad Proteins; C113580:U 0126; C031463:beta-glycerophosphoric acid