Nuclear factor-κB modulates osteogenesis of periodontal ligament stem cells through competition with β-catenin signaling in inflammatory microenvironments

Inflammation can influence multipotency and self-renewal of mesenchymal stem cells (MSCs), resulting in their awakened bone-regeneration ability. Human periodontal ligament tissue-derived MSCs (PDLSCs) have been isolated, and their differentiation potential was found to be defective due to beta-catenin signaling indirectly regulated by inflammatory microenvironments. Nuclear factor-kappa B (NF-kappa B) is well studied in inflammation by many different groups. The role of NF-kappa B needs to be studied in PDLSCs, although genetic evidences have recently shown that NF-kappa B inhibits osteoblastic bone formation in mice. However, the mechanism as to how inflammation leads to the modulation of beta-catenin and NF-kappa B signaling remains unclear. In this study, we investigated beta-catenin and NF-kappa B signaling through regulation of glycogen synthase kinase 3 beta activity (GSK-3 beta, which modulates beta-catenin and NF-kappa B signaling) using a specific inhibitor LiCl and a phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002. We identified that NF-kappa B signaling might be more important for the regulation of osteogenesis in PDLSCs from periodontitis compared with beta-catenin. BAY 11-7082 (an inhibitor of NF-kappa B) could inhibit phosphorylation of p65 and partly rescue the differentiation potential of PDLSCs in inflammation. Our data indicate that NF-kappa B has a central role in regulating osteogenic differentiation of PDLSCs in inflammatory microenvironments. Given the molecular mechanisms of NF-kappa B in osteogenic differentiation governed by inflammation, it can be said that NF-kappa B helps in improving stem cell-mediated inflammatory bone disease therapy. Cell Death and Disease (2013) 4, e510; doi:10.1038/cddis.2013.14; published online 28 February 2013