title: Differential response to CoCl2-stimulated hypoxia on HIF-1α, VEGF, and MMP-2 expression in ligament cells.
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.
authors.affiliation: Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, People's Republic of China.
authors.forename: Yequan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Tang
authors.forename: Ruyue
authors.initials: R
authors.lastname: Xue
authors.forename: Gurinder K
authors.initials: GK
authors.lastname: Singh
authors.forename: Wanqian
authors.initials: W
authors.lastname: Liu
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lv
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000328:Adult; D016118:Anterior Cruciate Ligament / Q000166:cytology*; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D003035:Cobalt; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D017888:Medial Collateral Ligament, Knee / Q000166:cytology*; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing; D055815:Young Adult
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C018021:cobaltous chloride