Damage or injury of the meniscus is associated with onset and progression of knee osteoarthritis (OA). The intrinsic repair
capacity of the meniscus is inhibited by inflammatory cytokines, such as interleukin-1 (IL-1). Using an in vitro meniscal
repair model system, we examined the hypothesis that inhibition of matrix metalloproteinases (MMPs) in the presence of IL-1
will enhance repair of meniscal lesions. Integrative repair of the meniscus was examined between two concentric explants cultured
with IL-1 and various MMP inhibitors for 14 days. Throughout the culture period, we assessed total specific MMP activity in
the media. At harvest, biomechanical testing to assess the strength of repair and histologic staining were performed. IL-1
decreased the shear strength of repair, as compared with control explants. In the presence of IL-1, the broad-spectrum MMP
inhibitor GM 6001 decreased the MMP activity in the media, increased the shear strength of repair, and enhanced tissue repair
in the interface. However, individual MMP inhibitors did not alter the shear strength of repair in either the presence or
absence of IL-1. These findings suggest IL-1 may inhibit meniscal repair through upregulation of MMPs, but inhibition of multiple
MMPs may be necessary to promote integrative meniscal repair.
One or more of the authors have received funding from the Arthritis Foundation (ALM, FG), VA Rehabilitation Research Service
Award (JBW), and NIH Grants AR50245 (FG), AG15768 (FG), AR48182 (FG), AR48852 (FG), and AR55434 (ALM).