TGF-β1 promoted MMP-2 mediated wound healing of anterior cruciate ligament fibroblasts through NF-κB.

Abstract

The adult human anterior cruciate ligament (ACL) has poor functional healing response. Transforming growth factor (TGF)-β1 enhances the wound repair by stimulating matrix proteins deposition as well as the proliferation and migration of cells. However, the function of the TGF-β1-induced matrix metalloproteinases' (MMPs) activities in the wound healing process is poorly understood. In this study, exogenous MMP-2 is added to mimic the TGF-β1-induced MMP-2 expression. Role of NF-κB pathway is further examined. Our results show that TGF-β1 induces dramatic elevation of MMP-2 activities and the MMP-2/tissue inhibitors of metalloproteinases ratio. Furthermore, the exogenous MMP-2 significantly promoted in vitro wound healing abilities of ACL fibroblasts that are significantly blocked with the addition of its inhibitors. TGF-β1 also increases the proliferation of ACL fibroblasts whereas MMP-2 alone does not, indicating that MMP-2 activities are not involved in the proliferation. TGF-β1-induced MMP-2 activity is inhibited by Bay11-7082 and Bay11-7085 (NF-κB inhibitors). Our results demonstrate that increased TGF-β1 facilitates the ACL healing process by promoting the fibroblasts migration and proliferation. The migration process is mediated by MMP-2 and NF-κB pathway is involved in TGF-β1-mediated MMP-2 release.

DOI: 10.3109/03008207.2010.516849
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@article{Wang2011TGF1PM, title={TGF-β1 promoted MMP-2 mediated wound healing of anterior cruciate ligament fibroblasts through NF-κB.}, author={Yequan Wang and Zhenyu Tang and Ruyue Xue and Gurinder K. Singh and Yonggang Lv and Kunning Shi and Kaiyong Cai and Linhong Deng and Li Yang}, journal={Connective tissue research}, year={2011}, volume={52 3}, pages={218-25} }