Figure 1.

OA-modifying effects by CRISPR-mediated ablation of NGF, IL-1β and MMP13. (A) Results of von Frey test on the mice receiving the PMM surgery and administration of AAV that expresses control or NGF-targeting sgRNAs. n=9. Unpaired Student’s t-test. (B) Representative histology images of osteoarthritic knee joints, which were collected 3 months after injections of control or NGF-targeting AAV. Yellow arrowheads, loss of AC; red arrowheads, osteochondrophytes; black arrowheads, synovial hyperplasia; green arrowheads, subchondral sclerosis. n=9. Scale bar, 200 μm. (C) OARSI scoring of knee joint AC destruction in the mice receiving the PMM surgery and control or NGF-targeting AAV. Both medial femoral condyle and medial tibial plateau were analysed on three-level sections of the joints and summed OARSI scores for the entire joint were presented. Unpaired Student’s t-test. n=9. (D) Representative μCT images of osteoarthritic knee joints, which were collected 3 months after injections of control or NGF-targeting AAV. Red arrowheads, osteophytes. n=9. Scale bar, 1 mm. (E,F) Representative histological and μCT results of osteoarthritic knee joints, which were collected three months after injections of IL-1β-targeting (E) or MMP13-targeting AAV (F). (G,H) Results of von Frey tests on the mice receiving the PMM surgery and administration of AAV that expresses IL-1β- (G) or MMP13-targeting AAV (H). Unpaired Student’s t-test, n=9. AAV, adeno-associated virus; AC, articular cartilage; IL-1β, interleukin-1β; MMP13, matrix metalloproteinase 13; NGF, nerve growth factor; OA, osteoarthritis; PMM, partial meniscectomy.