Open Access

ARTICLE

The Profile of MMP and TIMP in Injured Rat ACL

Ruyue Xue^*, Li Yang^*, Zhenyu Tang^*, Jin Zhang^*, YequanWang^*, Xinyan Tang^*, Jiahuan Jiang^*, Yupeng Wu^*, Ruifang Yang^*, Peter Chen^†, KL Paul Sun

* “111”project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China
† Departments of Bioengineering, University of California, San Diego, 9500Gilman Drive, La Jolla, CA 92093-0412, USA
‡ Department of Orthopaedics, University of California, San Diego
§ Corresponding Author. Bioengineering College, Chongqing University, Chongqing 400044, China. E-mail: klsung@ucsd.edu

Molecular & Cellular Biomechanics 2010, 7(2), 115-124. https://doi.org/10.3970/mcb.2010.007.115

Abstract

Human anterior cruciate ligament (ACL) has poor healing ability after injury. The devastating effects of matrix metalloproteinases (MMPs) excess expression are regarded as the main reason. Tissue inhibitor metalloproteinases (TIMPs) may be independent of MMPs inhibition. In this paper, a rat ACL rotating injury apparatus was designed to produce ACL injury. After inducing injury, joint fluids and ACL tissue total proteins were immediately extracted. In addition, ACL tissue was isolated in a culture plate with 1%FBS medium for the ex vivo study. We found MMP-2 in joint fluids increased significantly by 4 folds after ACL injury as a function of time. Ex vivo study showed MMP-2 in the medium and ACL cultured tissue increased significantly respectively to 3 folds and to 6 folds. The joint fluids global MMP increased to 3.5 folds with non-treatment and APMA-treatment in day three. On the gene expression level, the changes in MMP-1 and CD147 have the similar tendency. The ratio of MMP-1/TIMP-1 increased with time after ACL injury. We conclude that MMP-2 increased significantly in the early phase in the joint cavity after ACL injury. The ex vivo study demonstrated the same tendency. Generic MMP Activity Assay (global MMP assay) and zymography also showed significant increase in MMP activity in joint fluids. These results showed ACL having poor healing ability after injury may not be only due to ACL release of large quantities of MMPs. The important factor may be the alterations in the whole joint cavity's internal environment.

---