Glycogen Synthase Kinase 3ß inhibits BMSCs Chondrogenesis in Inflammation via the Cross-Reaction between NF-κB and ßCatenin 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 ss- (IL-1 ss-) induced inflammatory microenvironment. Glycogen synthase kinase-3 ss (GSK-3 ss) is an evolutionarily conserved serine/threonine kinase that plays a role in numerous cellular processes. The role of GSK-3 ss in inflammation may be related to the nuclear factor-kappa B (NF-kappa B) signaling pathway and the Wnt/ss-catenin signaling pathway, whose mechanism remains unclear. In this study, we found that GSK-3 ss can inhibit chondrogenesis of IL-1 ss-impaired BMSCs by disrupting metabolic balance and promoting cell apoptosis. By using the inhibitors LiCl and SN50, we demonstrated that GSK-3 ss regulates the chondrogenesis via the NF-kappa B and Wnt/ss-catenin signaling pathways and possibly mediates the cross-reaction between NF-kappa B and ss-catenin in the nucleus. Given the molecular mechanisms of GSK-3 ss in chondrogenic differentiation in inflammation, GSK-3 ss is a crucial target for the treatment of inflammation-induced cartilage disease.

Automated summary

Our study found that GSK-3β can inhibit chondrogenesis of IL-1β-impaired BMSCs through disrupting metabolic balance and promoting cell apoptosis, regulating chondrogenesis via the NF-κB and Wnt/β-catenin signaling pathways. GSK-3β may mediate the cross-reaction between NF-κB and β-catenin in the nucleus.