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

• Published in: Biomedicine & pharmacotherapy 2016-04, Vol.79, p.120-128
• Main Authors: Terencio, María Carmen, Ferrándiz, María Luisa, Carceller, María Carmen, Ruhí, Ramón, Dalmau, Pere, Vergés, Josep, Montell, Eulàlia, Torrent, Anna, Alcaraz, María José
• Format: Article
• Language: English
• Subjects: Animals; Anterior Cruciate Ligament - drug effects; Anterior Cruciate Ligament - pathology; Anterior Cruciate Ligament Injuries - drug therapy; Anterior Cruciate Ligament Injuries - pathology; Anterior cruciate ligament transection model; Biomarkers - blood; Bone and Bones - drug effects; Bone and Bones - pathology; Cartilage, Articular - drug effects; Cartilage, Articular - pathology; Chondroitin sulfate-glucosamine; Chondroitin Sulfates - pharmacology; Chondroitin Sulfates - therapeutic use; Disease Models, Animal; Drug Therapy, Combination; Female; Glucosamine - pharmacology; Glucosamine - therapeutic use; Inflammation Mediators - metabolism; Internal Medicine; Joints - drug effects; Joints - pathology; Medical Education; Osteoarthritis; Osteoarthritis, Knee - blood; Osteoarthritis, Knee - drug therapy; Osteoarthritis, Knee - pathology; Ovariectomised rats; Ovariectomy; Protective Agents - pharmacology; Protective Agents - therapeutic use; Rats, Wistar; X-Ray Microtomography
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.02.005

Abstract 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 μCT. Results CS-GlcN protected against cartilage degradation and reduced the levels of inflammatory mediators such as interleukin-1β and tumor necrosis factor-α 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 κB 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.