The Wnt/β-catenin and bone morphogenetic proteins(BMPs)pathways play important roles in controlling osteogenesis.Using a cell-based kinase inhibitor screening assay,we identified the compound bisin-doylmaleimide I(BI...The Wnt/β-catenin and bone morphogenetic proteins(BMPs)pathways play important roles in controlling osteogenesis.Using a cell-based kinase inhibitor screening assay,we identified the compound bisin-doylmaleimide I(BIM)as a potent agonist of the cyto-solicβ-catenin accumulation in preosteoblast cells.Through suppressing glycogen synthase kinase 3βenzyme activities,BIM upregulatedβ-catenin respon-sive transcription and extended duration of BMP initi-ated signal.Functional analysis revealed that BIM promoted osteoblast differentiation and bone formation.The treatment of human mesenchymal stem cells with BIM promoted osteoblastogenesis.Our findings pro-vide a new strategy to regulate mesenchymal stem cell differentiation by integration of the cellular signaling pathways.展开更多
基金supported by the Netherlands Organization for Scientific Research(NWO 918.66.066)Netherlands Initiative for Regenerative Medicine and Centre for Biomedical GeneticsNational Natural Science Foundation of China(Grant Nos.30900748 and 31171388)to H.H.
文摘The Wnt/β-catenin and bone morphogenetic proteins(BMPs)pathways play important roles in controlling osteogenesis.Using a cell-based kinase inhibitor screening assay,we identified the compound bisin-doylmaleimide I(BIM)as a potent agonist of the cyto-solicβ-catenin accumulation in preosteoblast cells.Through suppressing glycogen synthase kinase 3βenzyme activities,BIM upregulatedβ-catenin respon-sive transcription and extended duration of BMP initi-ated signal.Functional analysis revealed that BIM promoted osteoblast differentiation and bone formation.The treatment of human mesenchymal stem cells with BIM promoted osteoblastogenesis.Our findings pro-vide a new strategy to regulate mesenchymal stem cell differentiation by integration of the cellular signaling pathways.
