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

  • Stem Cells Int. 2022 Sep 12;2022:5670403. doi: 10.1155/2022/5670403.
Zhenggang Wang  1 ,  Zhiyi He  1 ,  Weikai Zhang  1 ,  Shuang Liang  1 ,  Kun Chen  2 ,  Shimeng Xu  1 ,  Ying Zhang  3 ,  Peng Cheng  1
Affiliations
  • 1. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2. Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
  • 3. Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
PMID: 36132167 DOI: 10.1155/2022/5670403
Abstract

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

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