Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
ISSN: 2157-7013
Wan-Ju Li, Andrew M. Handorf, Tsung-Lin Tsai and Matthew W. Squire
Scientific Tracks Abstracts: J Cell Sci Ther
Multipotent human mesenchymal stem cells (hMSCs) capable of diff erentiating into chondrocytes are considered a promising cell source for cartilage tissue engineering. While many studies have reported that chondrogenesis (CG) is regulated by biochemical molecules during hMSC diff erentiation, few have shown that treating pre-diff erentiation hMSCs with molecules, such as growth factors, aff ects subsequent CG. In this study, we investigated the molecular mechanisms by which fi broblast growth factor-2 (FGF-2) and glucose regulate the chondrogenic potential of pre-diff erentiation of hMSCs. Our results showed that FGF-2 pretreatment primed hMSCs for enhanced CG by reducing the expression of pluripotency genes and increasing Sox9 protein levels. Further, we showed that FGF-2 increased Sox9 protein levels in both proliferating and non-proliferating hMSCs, with proliferating hMSCs elevating Sox9 protein levels more dramatically. In addition, we demonstrated that glucose concentration in pre-diff erentiation culture aff ected the chondrogenic potential of hMSCs and subsequent CG by regulating the expression of phosphorylated PKC (pPKC) an d type II TGF-β receptor (TGFβRII) of the cells. High-glucose maintained hMSCs were less responsive to chondrogenic induction than low- glucose maintained cells due to the lower level of TGFβRII. By inhibiting the PKC activity of high-glucose maintained cells in pre-diff erentiation culture, TGFβRII of chondrogenic pellets was upregulated to enhance chondrogenesis. Taken together, our fi ndings provide new insights into the mechanism by which FGF-2 and glucose regulate pre-diff erentiation hMSCs to undergo enhanced CG
Wan-Ju Li is the principal investigator leading the Laboratory of Musculoskeletal Biology and Regenerative Medicine at the University of Wisconsin-Madison. He is an assistant professor in the Department of Orthopedics and Rehabilitation and the Department of Biomedical Engineering, and a faculty member in the Stem Cell and Regenerative Medicine Center and the Cellular and Molecular Biology Program. Dr. Li received his Ph.D. in Cell and Tissue Engineering from Thomas Jefferson University in 2004. He has received research awards from National Institutes of Health and North American Spine Society. Dr. Li has published more than 30 papers, including several highly cited papers, in the fi eld of stem cell and cartilage tissue engineering.