Effects of hypoxia pathway on multipotential differentiation of bone marrow stromal stem cells
Online published: 2011-07-27
Supported by
National Natural Science Foundation of China, 30872641;Shanghai Science and Technology Committee Foundation, 09DZ2200500,10DZ2211500;Technology Fund of Shanghai Jiaotong University School of Medicine, YZ1029
Objective To investigate the effects of hypoxia-inducible factor 1α(HIF-1α) on the multipotential differentiation of bone marrow stromal stem cells (MSCs) in the hypoxia pathway. Methods Conditional gene knockout of VHL gene of MSCs from transgenic mice was performed with Ad-Cre (gene knockout group), and control group was established (MSCs from transgenic mice infected with Ad-GPF). The expression of HIF-1α mRNA was detected by Real-Time PCR. Chondrogenic culture and osteogenic culture of MSCs were conducted for 14 d in two groups, and osteogenic culture of MSCs was conducted for 21 d in two groups, with culture of MSCs under 5% O2 in gene knockout group and culture of MSCs under 20% O2 in control group. The expression of chondrocyte marker of typeⅡcollagen (ColⅡ), adipocyte marker of peroxisome proliferator-activated receptors gamma (PPARγ) and osteoblast markers of osteocalcin (OC) and alkaline phosphatase (ALP) mRNA was detected by Real-Time PCR. The distributions of positive cells with ColⅡ staining and ALP staining were observed by light microscopy in two groups. Results The expression of HIF-1α mRNA in gene knockout group was significantly higher than that in control group (P<0.05). The expression of ColⅡ, PPARγ, OC and ALP mRNA in gene knockout group cultured under 5% O2 was significantly higher than that in control group cultured under 20% O2 (P<0.05). Compared with control group, the numbers of positive cells with ColⅡ staining and ALP staining were larger. Conclusion HIF-1α can promote the differentiation of MSCs into chondrocytes, adipocytes and osteoblasts under 5% O2.
ZENG Wen, ZHANG Wei, WANG Jun, et al . Effects of hypoxia pathway on multipotential differentiation of bone marrow stromal stem cells[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2011 , 31(7) : 913 . DOI: 10.3969/j.issn.1674-8115.2011.07.010
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