Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats

被引:24
作者
Carmen Terencio, Maria [1 ,2 ]
Luisa Ferrandiz, Maria [1 ,2 ]
Carmen Carceller, Maria [1 ,2 ]
Ruhi, Ramon [3 ]
Dalmau, Pere [3 ]
Verges, Josep [4 ]
Montell, Eulalia [4 ]
Torrent, Anna [4 ]
Jose Alcaraz, Maria [1 ,2 ]
机构
[1] Univ Valencia, Dept Pharmacol, Ave Vicent Andres Estelle S-N, E-46100 Valencia, Spain
[2] Univ Valencia, IDM, Ave Vicent Andres Estelle S-N, E-46100 Valencia, Spain
[3] Bioiberica SA, Technol Extract Dept, Mas Puigvert Crta N-2,Km 680-6, Barcelona 08389, Spain
[4] Bioiberica SA, PharmaSci Div, Preclin R&D Dept, Francesc Macia 7, Barcelona 08029, Spain
关键词
Anterior cruciate ligament transection model; Osteoarthritis; Chondroitin sulfate-glucosamine; Ovariectomised rats; KNEE OSTEOARTHRITIS; ARTICULAR-CARTILAGE; BIOLOGICAL MARKERS; IDENTIFY PATIENTS; GENE-EXPRESSION; BONE-RESORPTION; WILL RESPOND; HIGH-RISK; KAPPA-B; OSTEOPOROSIS;
D O I
10.1016/j.biopha.2016.02.005
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Context: The efficacy of the combination chondroitin sulfate-glucosamine (CS-GlcN) in the treatment of knee osteoarthritis (OA) has been suggested in recent clinical studies. In vitro reports have also suggested anti-inflammatory and anti-resorptive effects of this combination. Objective: The aim of this study was to characterize the effects of CS-GlcN on joint degradation in vivo including the assessment of inflammation and bone metabolism in a model of OA. Materials and methods: We have used the OA model induced by anterior cruciate ligament transection (ACLT) in ovariectomised rats. CS-GlcN was administered daily (oral gavage) from week 0 until week 12 after ovariectomy at the dose of 140 (CS) + 175 (GlcN)(HCl) mg/kg. Histochemical analyses were performed, the levels of biomarkers and inflammatory mediators were measured by luminex or ELISA and bone microstructure was determined by mu CT. Results: CS-GlcN protected against cartilage degradation and reduced the levels of inflammatory mediators such as interleukin-1 beta and tumor necrosis factor-a in the affected knee. In addition, serum biomarkers of inflammation and cartilage and bone degradation including matrix metalloproteinase-3, C-telopeptide of type II collagen and the ratio receptor activator of nuclear factor kappa B ligand/osteoprotegerin were significantly decreased by CS-GlcN. This treatment also tended to improve some bone microstructural parameters without reaching statistical significance. Discussion and conclusions: These results demonstrate the chondroprotective effects of CS-GlcN in vivo, in the experimental model of ACLT in ovariectomised rats, and suggest that this combination may be useful to control the joint catabolic effects of inflammatory stress. These findings could have clinical relevance related to the prevention of joint degradation by CS-GlcN and support the potential development of OA treatments based on this combination. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:120 / 128
页数:9
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