Canonical Notch signaling is required for bone morphogenetic protein ‐mediated human osteoblast differentiation

Bone morphogenetic protein (BMP) stimulation of bone ‐marrow‐derived human mesenchymal progenitor cells (hMSCs) increases Notch proteins via increased Notch ligand Jagged1 expression. Canonical Notch signaling is required for BMP‐induced ALPL expression and osteoblastic commitment of hMSCs. Both BMP‐induced osteoblastogenesis and Notch‐induc ed osteoblastogenesis require Runx2. AbstractOsteoblast differentiation of bone ‐marrow‐derived human mesenchymal stem cells (hMSC) can be induced by stimulation with canonical Notch ligand, Jagged1, or bone morphogenetic proteins (BMPs). However, it remains elusive how these two pathways lead to the same phenotypic outcome. Since Runx2 is regarded as a master regulator of osteoblastic differentiation, we targeted Runx2 with siRNA in hMSC. This abrogated both Jagged1 and BMP2 mediated osteoblastic differentiation, confirming the fundamental role for Runx2. However, while BMP stimulation increased Runx2 and downstream Osterix protein expression, Jagged1 treatment faile d to upregulate either, suggesting that canonical Notch signals require basal Runx2 expression. To fully understand the transcriptomic profile of differentiating osteoblasts, RNA sequencing was performed in cells stimulated with BMP2 or Jagged1. There was common upregulation ofALPL and extracellular matrix genes, such asACAN,HAS3,MCAM, andOLFML2B. Intriguingly, genes encoding components of Notch signaling (JAG1,HEY2, andHES4) were among the top 10 genes upregul...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research