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

摘要

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 β -catenin signaling indirectly regulated by inflammatory microenvironments. Nuclear factor- κ B (NF- κ B) is well studied in inflammation by many different groups. The role of NF- κ B needs to be studied in PDLSCs, although genetic evidences have recently shown that NF- κ B inhibits osteoblastic bone formation in mice. However, the mechanism as to how inflammation leads to the modulation of β -catenin and NF- κ B signaling remains unclear. In this study, we investigated β -catenin and NF- κ B signaling through regulation of glycogen synthase kinase 3 β activity (GSK-3 β , which modulates β -catenin and NF- κ B signaling) using a specific inhibitor LiCl and a phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002. We identified that NF- κ B signaling might be more important for the regulation of osteogenesis in PDLSCs from periodontitis compared with β -catenin. BAY 11-7082 (an inhibitor of NF- κ B) could inhibit phosphorylation of p65 and partly rescue the differentiation potential of PDLSCs in inflammation. Our data indicate that NF- κ B has a central role in regulating osteogenic differentiation of PDLSCs in inflammatory microenvironments. Given the molecular mechanisms of NF- κ B in osteogenic differentiation governed by inflammation, it can be said that NF- κ B helps in improving stem cell-mediated inflammatory bone disease therapy.