Differential expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in anterior cruciate ligament and medial collateral ligament fibroblasts after a mechanical injury: involvement of the p65 subunit of NF-kappaB.

The anterior cruciate ligament (ACL) is known to have a poor healing ability, especially in comparison with the medial collateral ligament, which can heal relatively well. In this study, we detected significant increases in the mRNA levels of multiple matrix metalloproteinases (MMPs) (MMP-1, -2, -7, -9, -11, -14, -17, -21, -23A, -24, -25, -27, and -28) and tissue inhibitors of metalloproteinases (TIMPs) (TIMP-1, -2, -3, and -4) in ACL fibroblasts after an in vitro injury with an equi-biaxial stretch chamber. However, only some MMPs (MMP-7, -9, -14, -21, and -24) showed increases in injured medial collateral ligament fibroblasts, and to a much lesser degree than that observed in the injured ACL fibroblasts. Zymography revealed a 6.3-fold increase of MMP-2 activity in injured ACL but not medial collateral ligament fibroblasts, which agrees with the global MMP activities assay. Bay-11 and curcumin can significantly decrease MMP-2 activities to 13% and 29% in injured ACL fibroblasts, respectively, which implies the involvement of p65 subunits of nuclear factor kappaB and AP-1 pathways. Furthermore, Bay-11 can decrease the global MMP activity released from injured ACL fibroblasts in a dose-dependent manner. In summary, the differential expression and activities of MMPs might help to explain the poor healing ability of ACL, and the p65 subunit of nuclear factor kappaB might be a potential target to facilitate the ACL repair.