Deletion of the Mmp13 gene in chondrocytes had no sig nificant effect on articular and sellectchem growth plate chondrocyte morphology. Tamoxifen was admi nistered to two week old Mmp13Col2ER mice and had no effect on articular and growth plate carti lage. MLI surgery was performed when the mice were 10 weeks old to induce OA. Knee joints were harvested 4, 8, 12, and Inhibitors,Modulators,Libraries 16 weeks post surgery. Histology showed that four weeks post MLI surgery, articular cartilage was nearly normal in both Mmp13Col2ER and Cre negative control groups. OA like fibrillation, clefting and cartilage loss down to the tidemark appeared 8 weeks post surgery and worsened at the 12 and 16 week time points in Cre negative control mice. In Mmp13Col2ER mice, however, there was markedly less articular cartilage excavation, especially at the 12 and 16 week time points.
Inhibitors,Modulators,Libraries OA grading likewise revealed significantly reduced carti lage degeneration at 8, 12 and 16 weeks post surgery in Mmp13Col2ER mice compared to the control group. To quantify OA progression, we performed histomor phometry using the OsteoMeasure system. The results showed that articular cartilage area and articular Inhibitors,Modulators,Libraries cartilage thickness at proximal tibiae, total cartilage area, and total cartilage thickness progressively decreased at 8, 12, and 16 weeks post surgery, but this progression was decelerated in Mmp13Col2ER mice compared to the control group. Articular cartilage area and articular carti lage thickness at proximal tibiae were significantly greater at 12 and 16 weeks post surgery in Mmp13Col2ER groups.
Total cartilage area was significantly differ ent at 16 weeks post surgery, and total carti lage thickness Inhibitors,Modulators,Libraries was significantly different at 8, 12, and 16 weeks post surgery. Articular cartilage area and thickness at distal femora had no significant changes at any time point post surgery. Col2 and proteoglycan loss and chondrocyte apoptosis are reduced in Mmp13Col2ER mice Safranin O Fast green staining and IHC of Col2 and ColX were performed on both Mmp13Col2ER and control mice eight weeks post surgery. The results showed greater proteoglycan and Col2 content in the Mmp13Col2ER mice. The results of IHC revealed increased ColX in both the Mmp13Col2ER and Cre negative control groups following MLI, but the injury associated induction was reduced in the Mmp13Col2ER mice.
To investigate chondro cytes apoptosis, we performed TUNEL staining on knee joints eight weeks Inhibitors,Modulators,Libraries post surgery in Mmp13Col2ER and control mice. best Results of TUNEL staining revealed that 28% of chondrocytes in articular cartilage underwent apoptosis in control mice that received MLI while only 6% of chondrocytes underwent apoptosis following MLI in Mmp13Col2ER mice. CL82198 decelerates MLI induced OA progression We used CL82198, a selective MMP13 inhibitor, to determine if inhibition of MMP13 activity can alter the progression of OA like degeneration in mice following MLI surgery.