Fig. 4: NGFR deficiency substantially reduces subchondral bone thickening and ectopic bone formation in osteoarthritic joints.

a Aggrecan-CreER efficiently targets multiple osteochondral tissues in the osteoarthritic joints, including articular cartilage (AC), subchondral area (SC), and meniscus (m). Arrowhead, targeted cells in SC. Scale bar, 100 μm. n = 3 joints. b NGFR was induced in osteoarthritic joints. Both control (Ngfr floxed) and KO (Ngfr^Acan-CreER) mice were injected with tamoxifen weekly to ablate Ngfr, starting 10 days after the DMM surgery. Arrowheads: NGFR⁺ osteochondral cells. Scale bar, 100 μm. n = 5. c NGFR loss downregulated subchondral and ectopic bone formation (arrowheads) in osteoarthritic joints. Scale bar, 200 μm. n = 12 mice. d Representative μCT 3D images of control and KO joints with OA. Arrowheads, ectopic bone. e Representative μCT 3D images of ectopic bone growth around cartilage, meniscus and synovium, as well as quantification of ectopic BV. Data are presented as mean values ± SD. n = 12 mice. Unpaired two-sided Student’s t-test. f Representative μCT 2D images of subchondral bone and BV/TV quantification of subchondral bone underneath medial tibial plateau (inside the red circles). #, ectopic bone outside subchondral area. Scale bars: 1 mm. Data are presented as mean values ± SD. n = 12 mice. Unpaired two-sided Student’s t-test. **p < 0.01, ****p < 0.0001. Source data are provided as a Source Data file.