Fig. 1

Chondrocytes produce Rankl under inflammation. a MLI surgery was performed on 12-week-old mice. After 4 weeks, articular cartilage was isolated from sham and MLI knee joints and gene expression of Rankl was measured (n = 4, *P = 0.050). Data are mean ± SEM. b Medial and lateral knee articular cartilage was isolated from patients undergoing TKA with medial compartment OA. Gene expression of human RANKL comparing more damaged medial cartilage to lateral cartilage (n = 5, *P = 0.031). Data are mean ± SEM. c Primary chondrocytes were cultured with IL-1β (10 ng·mL⁻¹) ± SC-514 (10 μmol·L⁻¹) for 24 h. Rankl gene expression was measured (Untreated vs IL-1β ***P = 0.000 2, IL-1β vs IL-1β + IKK2i ***P = 0.000 7), with data representing mean ± SEM of n = 4 independent experiments. d Rankl protein expression in IL-1β treated (24 h) chondrocytes. Data are mean ± SD for n = 2 representative replicates (***P = 0.003 3). e Two weeks post MLI, knee joints were fixed and sectioned for TRAP staining to identify osteoclasts in the subchondral region (arrows). f TRAP positive cells were counted in anterior and posterior compartments of femur and tibia in MLI and Sham joints (n = 8). (Sham Anterior Femur vs MLI Anterior Femur ***P = 0.002). Bars represent mean ± S.D. g MLI and sham surgeries were performed on right and left mouse knees, respectively. After 2 weeks, mice were sacrificed and joints were harvested and fixed. Bone volume/total volume of subchondral region was measured by uCT in same region of each mouse tibia (n = 5 mice) (*P = 0.036 5). h Representative image of subchondral slice from sham and MLI mouse joints displaying decreased bone volume (M and L indicate medial and lateral condyle, respectively)