Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee.

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Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids  Y.-H. Jean, M.D., Ph.D., Z.-H. Wen, Ph.D., Y.-C. Chang, M.S., S.-P. Hsieh, M.D., C.-C. Tang, Ph.D., Y.-H. Wang, Ph.D., C.-S. Wong, M.D., Ph.D.  Osteoarthritis and Cartilage  Volume 15, Issue 6, Pages 638-645 (June 2007) DOI: 10.1016/j.joca.2006.11.008 Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Experimental course. ACLT/S (n=8); ACLT/P (n=9); Naïve/P (n=6); and sham (arthrotomy without ACLT, n=9). Saline injection: intra-articular injection of 0.1ml of saline once a week for 5 consecutive weeks starting at week 8 after surgery. Parecoxib injection: as for the saline group, but using parecoxib (100μg/0.1ml). Osteoarthritis and Cartilage 2007 15, 638-645DOI: (10.1016/j.joca.2006.11.008) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Time-course of joint width changes after surgery. The widths of the bilateral hindlimb knee joints were measured in each rat before, and at 4, 8, 12, 16, and 20 weeks after surgery. The data (mean±s.e.m.) are expressed as the difference in knee width between the values at week 20 after surgery and before surgery in each group. a, P<0.05 compared to the Naïve/P and sham-operated groups; b, P<0.05 compared to the ACLT/S group. Osteoarthritis and Cartilage 2007 15, 638-645DOI: (10.1016/j.joca.2006.11.008) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Histopathological evaluation of cartilage of the medial femoral condyles (stain, Safranin-O/fast green; original magnification, 200×) and synovium (H/E stain, original magnification, 400×) of the knee at week 20 after surgery. (A) ACLT/S group showing surface fibrillation (arrow), chondrocyte loss, and a decrease in Safranin-O/fast green staining intensity, which extends into the radial zone. Cloning of chondrocytes is apparent in the transitional and radial zones. Decrease of Safranin-O/fast green staining in matrix and hyperplasia of chondrocytes in the calcified cartilage layer, and cleft and irregular bony trabeculum between junction of calcified cartilage and subchondral layer are observed. (B) ACLT/P group showing irregularity of the superficial layer of the cartilage (arrow), and mild loss of Safranin-O/fast green staining of the superficial layer of the cartilage. Recovery of proteoglycan and relative normality of chondrocytes in the calcified cartilage layer and smooth bony trabeculum in the subchondral layer are observed. In (C) Naïve/P and (D) sham groups, the superficial layer of cartilage is smooth and no disruption of surface integrity is observed (arrow). The cartilage matrix is well stained with Safranin-O/fast green. Preservation of Safranin-O/fast green staining and chondrocytes in calcified cartilage layer and smooth bony trabeculum is observed in subchondral layer. (E) Synovial membrane from the ACLT/S group, showing hyperplasia of lining cells and hypertrophy of the synovial and subsynovial tissue. Mononuclear cell infiltration of the underlying tissues and a fibrinoid exudate (arrow) are also seen. (F) Synovial membrane from the ACLT/P group shows focal synovitis (arrow) with mild mononuclear cell infiltration. Synovial membrane from the (G) Naïve/P and (H) sham groups shows no synovial lining cell hyperplasia (scale bar=100μm). Osteoarthritis and Cartilage 2007 15, 638-645DOI: (10.1016/j.joca.2006.11.008) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Glutamate and aspartate levels in joint dialysates of ACLT knees from the four groups. EAA levels in the knee joint dialysates were measured at week 20 after surgery. The dialysates were collected for 3h. The mean resting concentration of glutamate and aspartate in synovial fluid dialysates of the contralateral control rats were 2.01±0.15 and 0.33±0.02μM, respectively. The EAA concentrations in the contralateral knee, at week 20, were taken as the basal value (100%) and the glutamate (A) or aspartate (B) levels in the ACLT knee, Naïve/P or sham-operated knee are expressed as the % differences in EAA concentration from the basal 100%. Data are expressed as mean±s.e.m. a, P<0.05 compared to the Naïve/P and sham-operated groups; b, P<0.05 compared to the ACLT/S group. ACLT/S (n=8); ACLT/P (n=9); Naïve/P (n=6); and sham (n=9). Osteoarthritis and Cartilage 2007 15, 638-645DOI: (10.1016/j.joca.2006.11.008) Copyright © 2006 Osteoarthritis Research Society International Terms and Conditions