An “endocrine function of” bone to pick: starting with males

Zhao, Allan Z.; Su, Dongming

doi:10.1007/s13238-011-1035-0

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2012

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“…While targeted inhibition of osteoclasts with bisphosphonates has achieved success in preventing bone loss, searching factors to stimulate bone formation has been challenging (Rosen, 2003;Zhao and Su, 2011).…”

Section: Discussionmentioning

confidence: 99%

Bisindoylmaleimide I enhances osteogenic differentiation

2012

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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.

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Section: Discussionmentioning

confidence: 99%