Figure 1.

Reduced progression of arthritis following selective inhibition of membrane type 1 matrix metalloproteinase (MT1‐MMP) in mice with collagen‐induced arthritis (CIA). A, Collagen film degradation by human rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) in the absence or presence of 100 nM or 500 nM DX‐2400, 10 μM GM6001, or buffer (control). Clear, unstained areas indicate collagen degradation. B, Invasion of human RA FLS into the cartilage in the presence of buffer alone (control), 10 μM GM6001, or 100 nM or 500 nM DX‐2400. Arrows show invading FLS. C, Immunostaining for MT1‐MMP in the tarsometatarsal joints of a normal mouse and a mouse with CIA (10 days after arthritis onset). Bar = 200 μm. D, Clinical scores, paw swelling (first affected paw), and number of affected paws 10 days after the onset of arthritis in mice with CIA treated with IgG control or with 20 or 40 mg/kg of DX‐2400. Arrows indicate injection times. For the clinical scores and paw swelling data, values are the mean ± SEM of 22–23 mice per group. For the number of affected paws, each symbol represents an individual mouse; horizontal lines with bars show the mean ± SEM of 22–23 mice per group. ∗ = P < 0.05 for the indicated comparison or versus IgG control; ∗∗ = P < 0.01 versus IgG control. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/journal/doi/10.1002/art.39414/abstract