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Contrary to the pathways above, NOTCH signaling suppresses osteoblastogenesis as deletion of NOTCH1 and NOTCH2 or the critical transcription factor RBPJk in the embryonic limb mesenchyme enhanced osteoblast differentiation at the expense of bone marrow mesenchymal progenitors

causing dysbiosis and activation of inflammatory immune response by releasing IL-17 and other inflammatory signaling molecules consequently causing blood pressure elevation

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FIGURE 2 IGF SIGNALING IN THE CONTEXT OF LIGAND-RECEPTOR INTERACTIONS The IGF system is comprised of type I and type II receptors, their ligands (IGF-1 and IGF-2), IGFBPs, and IGFBP proteases (Le Roith et al., 2001)

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