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Differential response to CoCl2-stimulated hypoxia on HIF-1α, VEGF, and MMP-2 expression in ligament cells

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Abstract

The adult human anterior cruciate ligament (ACL) has a poor functional healing response, whereas the medial collateral ligament (MCL) does not. The difference in intrinsic properties of these ligament cells can be due to their different response to their located microenvironment. Hypoxia is a key environmental regulator after ligament injury. In this study, we investigated the differential response of ACL and MCL fibroblasts to hypoxia on hypoxia-inducible factor-1α, vascular endothelial growth factor, and matrix metalloproteinase-2 (MMP-2) expression. Our results show that ACL cells responded to hypoxia by up-regulating the HIF-1α expression significantly as compared to MCL cells. We also observed that in MCL fibroblasts response to hypoxia resulted in increase in expression of VEGF as compared to ACL fibroblasts. After hypoxia treatment, mRNA and protein levels of MMP-2 increased in both ACL and MCL. Furthermore we found in ACL pro-MMP-2 was converted more into active form. However, hypoxia decreased the percentage of wound closure for both ligament cells and had a greater effect on ACL fibroblasts. These results demonstrate that ACL and MCL fibroblasts respond differently under the hypoxic conditions suggesting that these differences in intrinsic properties may contribute to their different healing responses and abilities.

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Acknowledgments

This study was supported by the Innovation and Attracting Talents Program for College and University (‘111’ Project) (B06023), The Fundamental Research Funds for the Central Universities (CDJXS11231176), National Natural Science Foundation of China (11032012), and Key Science and Technology Program of CQ CSTC (2009AA5045).

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Authors and Affiliations

  1. Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People’s Republic of China

    Yequan Wang, Zhenyu Tang, Ruyue Xue, Gurinder K. Singh, Wanqian Liu, Yonggang Lv & Li Yang

  2. “111” Biomechanics and Tissue Repair Laboratory, Bioengineering College, Chongqing University, Chongqing, 400044, China

    Yequan Wang, Zhenyu Tang, Ruyue Xue, Gurinder K. Singh, Wanqian Liu, Yonggang Lv & Li Yang

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  1. Yequan Wang
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  2. Zhenyu Tang
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  3. Ruyue Xue
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  4. Gurinder K. Singh
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  5. Wanqian Liu
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  6. Yonggang Lv
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  7. Li Yang
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Correspondence to Li Yang.

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Wang, Y., Tang, Z., Xue, R. et al. Differential response to CoCl2-stimulated hypoxia on HIF-1α, VEGF, and MMP-2 expression in ligament cells. Mol Cell Biochem 360, 235–242 (2012). https://doi.org/10.1007/s11010-011-1061-5

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  • DOI: https://doi.org/10.1007/s11010-011-1061-5

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