Regulation of Mesenchymal Stem Cell Chondrogenesis by Glucose Through Protein Kinase C/Transforming Growth Factor Signaling.
Regulation of Mesenchymal Stem Cell Chondrogenesis by Glucose through Protein Kinase C/Transforming Growth Factor Signaling.
Filed under: Rehab Centers
Osteoarthritis Cartilage. 2012 Nov 11;
Tsai TL, Manner PA, Li WJ
OBJECTIVE: Effective induction of human mesenchymal stem cell (hMSC) differentiation for regenerative medicine applications remains a great challenge. While much research has studied hMSC activity during differentiation, it is unclear whether pre-differentiation culture can modulate differentiation capacity. We investigate the effect of glucose concentration in pre-differentiation/expansion culture on modulating chondrogenic capacity of hMSCs, and explore the underlying molecular mechanism. DESIGN: The extent of chondrogenesis of hMSCs previously cultured with different concentrations of glucose was evaluated. Transforming growth factor-beta (TGF-?) signaling molecules and protein kinase C (PKC) were analyzed to identify the role of these molecules in the regulation of glucose on chondrogenesis. In addition, hMSCs in high-glucose expansion culture were treated with the PKC inhibitor to modulate the activity of PKC and TGF-? signaling molecules. RESULTS: High-glucose maintained hMSCs were less chondrogenic than low-glucose maintained cells upon receiving differentiation signals. Interestingly, we found that high-glucose culture increased the phosphorylation of PKC and expression of type II TGF-? receptor (TGF?RII) in pre-differentiation hMSCs. However, low-glucose maintained hMSCs became more responsive to chondrogenic induction with increased PKC activation and TGF?RII expression than high-glucose maintained hMSCs during differentiation. Inhibiting the PKC activity of high-glucose maintained hMSCs during expansion culture upregulated the TGF?RII expression of chondrogenic cell pellets, and enhanced chondrogenesis. CONCLUSION: Our findings demonstrate the effect of glucose concentration on regulating the chondrogenic capability of pre-differentiation hMSCs, and provide insight into the mechanism of how glucose concentration regulates PKC and TGF-? signaling molecules to prime pre-differentiation hMSCs for subsequent chondrogenesis.
HubMed – rehab
Neuropsychological Rehabilitation Volume 22, 2012, List of Reviewers.
Filed under: Rehab Centers
Neuropsychol Rehabil. 2012 Dec; 22(6): 960
Neuropsychological Rehabilitation Volume 22, 2012, List of Contents.
Filed under: Rehab Centers
Neuropsychol Rehabil. 2012 Dec; 22(6): 954-957
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