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. 2012 May 2;3(4):311–320. doi: 10.1007/s13238-012-2027-4

Bisindoylmaleimide I enhances osteogenic differentiation

Fangfang Zhou 1,2, Huizhe Huang 2,✉, Long Zhang 1,✉
PMCID: PMC4875475  PMID: 22549588

Abstract

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 bisindoylmaleimide I (BIM) as a potent agonist of the cytosolic β-catenin accumulation in preosteoblast cells. Through suppressing glycogen synthase kinase 3β enzyme activities, BIM upregulated β-catenin responsive transcription and extended duration of BMP initiated 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 provide a new strategy to regulate mesenchymal stem cell differentiation by integration of the cellular signaling pathways.

Keywords: bisindoylmaleimide I, Wnt/β-catenin, glycogen synthase kinase 3β, bone morphogenetic protein, human mesenchymal stem cells (hMSCs), osteogenesis

Contributor Information

Huizhe Huang, Email: devbiology@cqmu.edu.cn.

Long Zhang, Email: L.Zhang@lumc.nl.

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