Figure 5

Comparative activity of NBI-31772, a small-molecule inhibitor of the binding of insulin-like growth factor (IGF)-1 to IGF-binding proteins (IGFBPs), in primary cultured human osteoarthritic chondrocytes incubated with IGF-1 or R³ IGF-1 (an analog of IGF-1 with a greatly reduced affinity for IGFBPs). Chondrocytes were incubated with (a,c) 3.3 nM IGF-1 or (b,d) 3.3 nM R³ IGF-1 for 24 hours; NBI-31772 (0.1–10 μM) was added and the cells were incubated for 24 more hours in the presence of 1.5 μCi/ml Na[³⁵SO₄]. (a,b) Total proteoglycan synthesis and (c,d) cell-associated proteoglycans, calculated from the ratio of ³⁵S-labeled proteoglycans remaining in the cell layer over total proteoglycans. Data are expressed as the means and SEM of four replicates from a representative experiment (out of four independent cultures). Statistical differences between groups containing NBI-31772 plus IGF-1 or R³ IGF-1 and the respective control groups (IGF-1 or R³ IGF-1) were measured using Student's t-test. *P < 0.05; ***P < 0.001.