Skip to main content
Fig. 4 | Stem Cell Research & Therapy

Fig. 4

From: Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways

Fig. 4

1. Osteoprotegerin (OPG) inhibits binding of RANKL to RANK. RANKL-RANK binding results in trimerization of the receptor. This, in turn triggers activation of tumor necrosis factor receptor-associated factor (TRAF)-6 and activation of the subsequent pathways. All of the above-mentioned steps are necessary for osteoclast differentiation. High concentrations of OPG result in inhibition of the pathway and thus negatively regulate osteoclast differentiation [39]. 2. Rho is a family of proteins which act in actin polymerization. Activation of this pathway results in activation of Rho-associated coiled coil-containing protein kinase (ROCK) and mammalian Diaphanous (mDia). Furthermore, ROCK is known as the phosphorylator of LIM motif-containing protein kinase (LIMK). LIMK is strongly associated with bone mass and osteoblast differentiation. Therefore, initiation of Rho signaling pathway positively regulates osteogenic differentiation. 3. Molecules that activate the hedgehog signaling pathway bind to patched receptor (PTCH). Without the presence of hedgehog ligands, The PTCH inhibits Smoothened (SMO). Ligand-PTCH binding results in Termination of this inhibition. Followed by this, glioma-associated oncogene transcription factor (GLI) is released and translocated into the nucleus which increases transcription of target genes [40]. 4. Sirt1 is a deacetylator of various transcription factors. FOXO3A is one of the transcription factors it acetylates. FOXO3A is a key regulator of stress resistance gene transcription which also mediates osteogenic differentiation. Another downstream pathway of Sirt1 is Bmi-1. Sirt1 activation has been found to result in increased binding of Sirt1 and Bmi-1 and thus contributing to osteogenic gene expression

Back to article page