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Establishment of a rabbit model to study the influence of advanced glycation end products accumulation on osteoarthritis and the protective effect of pioglitazone Y. Li, Y. Zhang, C. Chen, H. Zhang, C. Ma, Y. Xia Osteoarthritis and Cartilage Volume 24, Issue 2, Pages (February 2016) DOI: /j.joca Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions
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Fig. 1 (a) Effects of d-ribose on AGEs expression in synovial fluid. Rabbits were injected with d-ribose (123 mmol/L, 350 mmol/L, 1000 mmol/L) for 7 weeks, applying physical exercise at the same time. The expression of AGEs was quantified by ELISA. Data are expressed as means ± SD (n = 8). **P < 0.001 vs PBS control. The macroscopic observations of cartilage from the femoral condyles (b,d,f,h) and tibial plateaus (c,e,g,i) of each group at 7th day after 7 weeks' i.a. injection. Right rabbit stifle of the PBS control group (b,c), low-dose (123 mmol/l d-ribose) group (d,e), moderate-dose (350 mmol/l d-ribose) group (f,g), high-dose (1000 mmol/l d-ribose) group (h,i). The removal of soft tissues and ligaments allows the gross examination of the articular surfaces. Erosion and pitting (areas indicated by white arrow) of the condyles and plateaus were evident in the rabbits with OA. In the d-ribose injected rabbits, a increase in the severity of lesions on the plateaus was seen, particularly after a dosage of 1000 mmol/l. Histologic analysis of representative sections of osteoarthritic (OA) cartilage from the tibial plateaus of d-ribose i.a. injected rabbits with OA. (j) control group (PBS); (k) low-dosage group (123 mmol/l d-ribose); (l) moderate-dosage group (350 mmol/l d-ribose); (m) high-dosage group (1000 mmol/l d-ribose). (Safranin-o-fast green-stained; original magnification ×200). Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions
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Fig. 2 Effects of AGEs on TNF-α, MMP-13 and PPARγ expression in synovial fluid or cartilage. AGEs levels increased by injecting d-ribose (123 mmol/L, 350 mmol/L, 1000 mmol/L) for 7 weeks. The expression of TNF-α in synovial fluid (a), cartilage (b), MMP-13 in synovial fluid (c), cartilage (d) and PPARγ in synovial fluid (e) was quantified by ELISA. Data are expressed as means ± SD (n = 8). **P < 0.001 vs PBS control. Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions
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Fig. 3 AGEs expression in synovial fluid of the two groups (a). Rabbits were treated with placebo and pioglitazone at the dose of 20 mg/kg/day orally and i.a. injected with d-ribose (1000 mmol/l) for 7 weeks, applying physical exercise at the same time. The expression of AGEs was quantified by ELISA. Data are expressed as means ± SD (n = 8). Macroscopic appearance of cartilage from femoral condyle and tibial plateaus of pioglitazone-treated group (b,c), placebo-treated group (d,e). Erosion and pitting (areas indicated by white arrow) were evident in the OA animals. In the pioglitazone-treated animals, the lesions were less severe compared with those in the placebo-treated controls. Histologic analysis of representative sections of osteoarthritic (OA) cartilage from the tibial plateaus of pioglitazone-treated (f) and placebo-treated (g) rabbits with OA (Safranin-o-fast green-stained; original magnification ×200). Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions
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Fig. 4 Effects of pioglitazone on the AGE-Induced TNF-α and MMP-13 expression in synovial fluid and cartilage. The expression of TNF-α in synovial fluid (a), cartilage (b) and MMP-13 in synovial fluid (c), cartilage (d) was quantified by ELISA. Data are expressed as means ± SD (n = 8). **P < 0.001 vs placebo control. Osteoarthritis and Cartilage , DOI: ( /j.joca ) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions
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