Figure 5.

Blocking of low‐density lipoprotein receptor–related protein 1 (LRP‐1) sheddases restores endocytic capacity and reduces aggrecan and collagen degradation in osteoarthritic (OA) cartilage. A, Recovery of endocytic capacity in OA chondrocytes upon treatment with anti–ADAM‐17 and anti–matrix metalloproteinase 14 (anti–MMP‐14) antibodies (Ab). Endocytosis of ADAMTS‐5 (10 nM) was measured as described in Figures 1H and I (n = 3 donors). B and C, Inhibition of aggrecan and collagen degradation in human OA cartilage upon treatment with combined anti–ADAM‐17 and anti–MMP‐14 antibodies. OA knee cartilage explants were incubated with antibodies or tissue inhibitor of metalloproteinases (TIMP) at 250 nM. B, Aggrecan degradation detected after 48 hours with an antibody against the aggrecan neoepitope ³⁷⁴ARGSV. The mean value in medium of the cartilage incubated with the control antibodies was set at 100 (dashed line) (n = 8 donors). C, Collagen degradation of cultured OA cartilage after 96 hours of incubation, measured by hydroxyproline assay. The amount of hydroxyproline released with control antibodies was set at 100 (dashed line). In A, values are the mean ± SD. In B and C, symbols represent individual cartilage donors; bars show the mean ± SD. The mean values in media of the cartilage incubated with the control antibodies for 48 hours (B) or 96 hours (C) were set at 100 (dashed lines). ∗ = P < 0.05, by Student's 2‐tailed t‐test (A) or one‐way analysis of variance followed by Dunnett's multiple comparison test (C). RAP = receptor‐associated protein; N‐TIMP‐3 = N‐terminal domain of human TIMP‐3.