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

Abstract

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

• Authors: X Chen, C Hu, G Wang, L Li, X Kong, Y Ding, Y Jin
• Journal: Cell death & disease (Cell Death Dis) Vol. 4 Pg. e510 (Feb 28 2013) ISSN: 2041-4889 [Electronic] England
• PMID: 23449446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(4-methylphenylsulfonyl)-2-propenenitrile
• Chromones
• Morpholines
• NF-kappa B
• Nitriles
• Phosphoinositide-3 Kinase Inhibitors
• RNA, Messenger
• Sulfones
• Transcription Factor RelA
• beta Catenin
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Glycogen Synthase Kinase 3
• Lithium Chloride

Topics

• Adult
• Animals
• Cell Differentiation (drug effects)
• Cells, Cultured
• Cellular Microenvironment
• Chromones (pharmacology)
• Glycogen Synthase Kinase 3 (antagonists & inhibitors, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Inflammation (pathology)
• Lithium Chloride (pharmacology)
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Morpholines (pharmacology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitriles
• Osteogenesis
• Periodontal Ligament (cytology, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• RNA, Messenger (metabolism)
• Signal Transduction
• Sulfones
• Transcription Factor RelA (genetics, metabolism)
• Wnt Signaling Pathway
• beta Catenin (metabolism)