Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University , Chongqing , PR China.
Connect Tissue Res. 2011 Jun;52(3):218-25. doi: 10.3109/03008207.2010.516849. Epub 2010 Oct 8.
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.
成人前交叉韧带（ACL）的功能愈合反应较差。转化生长因子（TGF）-β1 通过刺激基质蛋白沉积以及细胞增殖和迁移来增强伤口修复。然而，TGF-β1 诱导的基质金属蛋白酶（MMPs）活性在伤口愈合过程中的功能尚不清楚。在这项研究中，添加外源性 MMP-2 来模拟 TGF-β1 诱导的 MMP-2 表达。进一步研究了 NF-κB 通路的作用。我们的结果表明，TGF-β1 诱导 MMP-2 活性和 MMP-2/金属蛋白酶组织抑制剂的比率显著升高。此外，外源性 MMP-2 显著促进 ACL 成纤维细胞的体外伤口愈合能力，而添加其抑制剂则显著阻断。TGF-β1 还增加了 ACL 成纤维细胞的增殖，而 MMP-2 本身不会，表明 MMP-2 活性不参与增殖。Bay11-7082 和 Bay11-7085（NF-κB 抑制剂）抑制 TGF-β1 诱导的 MMP-2 活性。我们的结果表明，增加的 TGF-β1 通过促进成纤维细胞迁移和增殖来促进 ACL 愈合过程。迁移过程由 MMP-2 介导，NF-κB 通路参与 TGF-β1 介导的 MMP-2 释放。
