Glycogen Synthase Kinase 3 β inhibits BMSCs Chondrogenesis in Inflammation via the Cross-Reaction between NF- κ B and β -Catenin in the Nucleus.

Inflammation can influence the pluripotency and self-renewal of mesenchymal stem cells (MSCs), thereby altering their cartilage regeneration ability. Sprague-Dawley (SD) rat bone marrow mesenchymal stem cells (BMSCs) were isolated and found to be defective in differentiation potential in the interleukin-1 β- (IL-1 β -) induced inflammatory microenvironment. Glycogen synthase kinase-3 β (GSK-3 β ) is an evolutionarily conserved serine/threonine kinase that plays a role in numerous cellular processes. The role of GSK-3 β in inflammation may be related to the nuclear factor- κ B (NF- κ B) signaling pathway and the Wnt/ β -catenin signaling pathway, whose mechanism remains unclear. In this study, we found that GSK-3 β can inhibit chondrogenesis of IL-1 β -impaired BMSCs by disrupting metabolic balance and promoting cell apoptosis. By using the inhibitors LiCl and SN50, we demonstrated that GSK-3 β regulates the chondrogenesis via the NF- κ B and Wnt/ β -catenin signaling pathways and possibly mediates the cross-reaction between NF- κ B and β -catenin in the nucleus. Given the molecular mechanisms of GSK-3 β in chondrogenic differentiation in inflammation, GSK-3 β is a crucial target for the treatment of inflammation-induced cartilage disease.