Fig. 3

Bone particles drive the production of catabolic genes via NF-κB. a Chondrocytes from NF-κB luciferase reporter mice were cultured with BP or IL-1β for 24 h. Luciferase assay was performed to measure NF-κB activation (Untreated vs IL-1β ****P < 0.000 1, Untreated vs BP **P = 0.001, n = 4 independent replicates). Results are mean ± SD from one of three representative experiments. b, c IKK2^−/− chondrocytes were transduced with adeno-GFP or adeno-cre. Cells were then cultured with BP for 24 h. Il-6 and Mmp13 gene expression was measured (IL-6: GFP + BP vs IKK2^−/− + BP ^****P < 0.000 1. MMP13: GFP + BP vs IKK2^−/− + BP ****P < 0.000 1). Results are mean ± SD for n = 4 replicates. d MLI surgery was performed on 12-week-old mice. IKK2 inhibitor was injected I.P. for 6 weeks and joints were harvested for histology to perform safranin-O staining, with most damage to tibial surface (arrows). Representative images are displayed. e Blinded OARSI scoring was performed to grade OA severity on the tibial surface (Sham + Vehicle vs MLI + Vehicle ****P < 0.000 1, MLI + Vehicle vs MLI + IKK2i ****P < 0.000 1). Bars represent mean ± SEM. from n = 4 vehicle treated and n = 3 inhibitor treated mice. f IHC was performed for Mmp13 in articular cartilage of joint sections under the same conditions. Representative images are displayed