Apoptosis in chondrogenesis of human mesenchymal stem cells: effect of serum and medium supplements |
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Authors: | Chien-Yuan Wang Ling-Lan Chen Pei-Yin Kuo Jia-Ling Chang Yng-Jiin Wang " target="_blank">Shih-Chieh Hung |
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Institution: | (1) Stem Cell Laboratory, Department of Medical Research and Education, Veterans General Hospital-Taipei, 201, Sec. 2, Shih-Pai Road, Taipei, 11217, Taiwan;(2) Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, 112, Taiwan;(3) Institute of Biomedical Engineering, National Yang-Ming University, Taipei, 112, Taiwan;(4) Clinical Medicine, National Yang-Ming University, Taipei, 112, Taiwan;(5) Pharmacology, National Yang-Ming University, Taipei, 112, Taiwan;(6) Ton Yen General Hospital, Hsinchu, Taiwan; |
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Abstract: | Apoptosis is an inevitable process during development and is evident in the formation of articular cartilage and endochondral
ossification of growth plate. Mesenchymal stem cells (MSCs) can serve as alternative sources for cell therapy in focal chondral
lesions or diffuse osteoarthritis. But there are few, if any, studies investigating apoptosis during chondrogenesis by MSCs.
The aim of this study was to find the better condition to prevent apoptosis during chondrogenesis by MSCs. Apoptosis were
evaluated in MSCs induced in different chondrogenic media by the use of Annexin V, TUNEL staining, lysosomal labeling with
lysotracker and immunostaining of apoptotic markers. We found apparent apoptosis was demonstrated by Annexin V, TUNEL staining
and lysosomal labeling during chondrogenesis. Meanwhile, the degree of apoptosis was related to the reagents of the defined
chondrogenic medium. Adding serum in medium increased apoptosis, however, TGF-β1 inhibited apoptosis. The apoptosis was associated
with the activation of caspase-3, the increase in the Bax/Bcl-2 ratio, the loss of lysosomal integrity, and the increase of
PARP-cleavage. Pro-inflammatory cytokines, IL-1α, IL-1β and TNFα did not induce any increase in apoptosis. Interestingly,
the inhibition of apoptosis by serum free medium supplemented with ITS was also associated with an increase in the expression
of type II collagen, and a decrease in the expression of type X collagen, Runx2, and other osteogenic genes, while TGF-β1
increased the expression of Sox9, type II and type X collagen and decreased the expression of osteogenic genes. These data
suggest apoptosis occurs during chondrogenesis by MSCs by cell death intrinsic pathway activation and this process may be
modulated by culture conditions. |
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