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. 2017 Apr 28;69(6):1246–1256. doi: 10.1002/art.40080

Figure 4.

Figure 4

Combination of antibodies inhibiting ADAM‐17 and matrix metalloproteinase 14 (MMP‐14) blocks shedding of low‐density lipoprotein receptor–related protein 1 (LRP‐1) in osteoarthritic (OA) cartilage. A, Results of culturing human normal chondrocytes (n = 3 donors) with Dulbecco's modified Eagle's medium without (None) or with 10 ng/ml interleukin‐1 (IL‐1) in the absence or presence of combined anti–ADAM‐17 and anti–MMP‐14 (10–200 nM each) for 48 hours. LRP‐1 proteins in the cell lysate were analyzed by Western blotting with antibodies against α‐ and β‐chains of LRP‐1. B, Effect of combining anti–MMP‐14 and anti–ADAM‐17 antibodies (200 nM each) on LRP‐1 shedding in human OA chondrocytes (n = 5 donors). C, Time course analysis of the effect of combined anti–MMP‐14 and anti–ADAM‐17 antibodies on the recovery of cellular LRP‐1. D, Effect of combined anti–MMP‐14 and anti–ADAM‐17 antibodies on LRP‐1 shedding in human knee OA cartilage explants (n = 6 donors each). In A, values are the mean ± SD, and the mean value in the cells incubated without IL‐1 or the antibodies was set at 1 (dashed line). In B–D, symbols represent individual cartilage donors; bars show the mean ± SD. In B–D, the mean values in the cells or cartilage incubated with the control antibodies for 8 hours (C) or 24 hours (B and D) were set at 1 (dashed lines). ∗ = P < 0.05, by Student's 2‐tailed t‐test.