Figure 1.

Decelerated osteoarthritis progression in Mmp13^Col2ER mice. Tamoxifen was administered when matrix metalloproteinase (MMP13) conditional knockout (cKO) mice (Mmp13^Col2ER) and Cre-negative control mice were two weeks old (1 mg/10 g body weight, i.p., daily for five days). Meniscal-ligamentous injury (MLI)-induced osteoarthritis (OA) surgery was performed on the right hind-limbs when the mice were 10 weeks old. The left hind-limbs were used as sham controls. (A) Knee joint samples were harvested 4, 8, 12, or 16 weeks post-surgery and Alcian blue/Hematoxylin/Orange G staining was performed. Histological results showed decreased articular cartilage degradation in Mmp13^Col2ER mice 8, 12 and 16 weeks post-surgery. (B) Histological grading by blinded observers confirmed decreased articular cartilage degradation in Mmp13^Col2ER mice at 8, 12, and 16 weeks compared to control Cre-negative mice (*P < 0.05). (C) Tibia articular cartilage area was quantified by tracing the Alcian blue-positive area in the proximal tibia. There was no significant difference 4 and 8 weeks post-surgery in Mmp13^Col2ER MLI mice versus control MLI mice. The tibia cartilage area was increased 21% in Mmp13^Col2ER MLI mice compared to control MLI mice 12 weeks post-surgery (*P < 0.05) and increased 31% 16 weeks post-surgery (*P < 0.05). (D) Tibia thickness was quantified by tracing the Alcian blue-positive thickness in the center of the tibial plateau. There was no significant difference in tibial cartilage thickness at 4 or 8 weeks post-surgery. Tibia cartilage thickness was increased 29% in Mmp13^Col2ER MLI mice compared to control MLI mice 12 weeks post-surgery (*P < 0.05) and increased 50% 16 weeks post-surgery (*P < 0.01). (E) Total articular cartilage area was quantified by tracing the Alcian blue-positive area in both the proximal tibia and distal femur. No significant differences were detected 4, 8, and 12 weeks post-surgery. Total cartilage area increased 18% in Mmp13^Col2ER MLI mice compared to control MLI mice 16 weeks post-surgery (*P < 0.01). (F) Total cartilage thickness was quantified by tracing the Alcian blue-positive thickness in the center of the proximal tibia and distal femur. No significant differences were detected at 4, 8, and 12 weeks post-surgery. Total cartilage thickness increased 39% in Mmp13^Col2ER MLI mice compared to control MLI mice 16 weeks post-surgery (*P < 0.01).