Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

• DOI: 10.1096/fj.201802137rrr
• Publication Date: 2019-01-29T20:35:34Z
• Authors: Hui Jing; Xiaoyang Zhang; Manchen Gao; Kai Luo; Wei Fu; Meng Yin; Wei Wang; Zhongqun Zhu; Jinghao Zheng; Xiaomin He
• Keywords: Chondrogenesis; RUNX2; Aggrecan; SOX9

Cartilage engineering strategies using mesenchymal stem cells (MSCs) could provide preferable solutions to resolve long-segment tracheal defects. However, the drawbacks of widely used chondrogenic protocols containing TGF-β3, such as inefficiency and unstable cellular phenotype, are problematic. In our research, optimize differentiation human umbilical cord MSCs (hUCMSCs), kartogenin (KGN) preconditioning was performed prior TGF-β3 induction. hUCMSCs were preconditioned with 1 µM KGN for 3 d, sequentially pelleted, incubated 28 d. Then, expression chondrogenesis- ossification-related genes evaluated by immunohistochemistry RT-PCR. The underlying mechanism governing beneficial effects explored phosphorylated kinase screening validated in vitro vivo JNK inhibitor (SP600125) β-catenin activator (SKL2001). After preconditioning, fibroblast growth factor receptor 3, a marker precartilaginous cells, up-regulated hUCMSCs. Furthermore, KGN-preconditioned efficiently differentiated into chondrocytes elevated gene (SOX9, aggrecan, collagen II) reduced ossifie (collagen X MMP13) compared treated only. Phosphokinase indicated that directly related an up-regulation phosphorylation suppression levels. Blocking activating tests revealed prochondrogenic achieved mainly JNK/Runt-related transcription (RUNX)1 pathway, antiossific imparted suppressing β-catenin/RUNX2 pathway. Eventually, patches, based on encapsulated electrospun poly (l-lactic acid-co-ε-caprolactone)/collagen nanofilms, successfully restoring defects rabbit models. summary, likely improves committing them stage enhanced suppressed β-catenin. This novel protocol consisting subsequent induction might be cartilage MSCs.—Jing, H., Zhang, X., Gao, M., Luo, K., Fu, W., Yin, Wang, Zhu, Z., Zheng, J., He, X. Kartogenin commits potential modulating β-catenin—related pathways. FASEB J. 33, 5641–5653 (2019). www.fasebj.org