Double edged sword effect of IL 1b on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF kB, MAPK and BMP/Smad signaling pathways
Microenvironmental conditions can interfere with the functional role and differentiation of mesenchymal stem cells (MSCs) Recent studies suggest that an inflammatory microenvironment can significantly impact the osteogenic potential of periodontal ligament stem cells (PDLSCs) but the precise effects and mechanisms involved remain unclear. Here, we show for the first time that interleukin 1b (IL 1b) has dual roles in the osteogenesis of PDLSCs at concentrations ranging from physiologically healthy levels to those found in chronic periodontitis. Low doses of IL 1b activate the BMP/Smad signaling pathway to promote the osteogenesis of PDLSCs, but higher doses of IL 1b inhibit BMP/Smad signaling through the activation of nuclear factor kB (NF kB) and mitogen activated protein kinase (MAPK) signaling, inhibiting osteogenesis. These results demonstrate that crosstalk between NF kB, MAPK and BMP/Smad signaling mediates this dual effect of IL 1b on PDLSCs. We also show that the impaired osteogenesis of PDLSCs results in more inflammatory cytokines and chemokines being released, inducing the chemotaxis of macrophages, which further clarifies the role of PDLSCs in the pathogenesis of periodontitis.
Cell Death and Disease