title: Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellé s/n, 46100 Burjasot, Valencia, Spain.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Terencio
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellé s/n, 46100 Burjasot, Valencia, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Ferrándiz
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellé s/n, 46100 Burjasot, Valencia, Spain.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Carceller
authors.affiliation: Technological Extraction Department, Bioiberica S.A., Pol. Ind. "Mas Puigvert" Crta. N-II, Km 680.6, 08389 Palafolls, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Ruhí
authors.affiliation: Technological Extraction Department, Bioiberica S.A., Pol. Ind. "Mas Puigvert" Crta. N-II, Km 680.6, 08389 Palafolls, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Dalmau
authors.affiliation: Pre-Clinical R&D Department, PharmaScience Division, Bioiberica S.A., Francesc Macià 7, 08029 Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Vergés
authors.affiliation: Pre-Clinical R&D Department, PharmaScience Division, Bioiberica S.A., Francesc Macià 7, 08029 Barcelona, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Montell
authors.affiliation: Pre-Clinical R&D Department, PharmaScience Division, Bioiberica S.A., Francesc Macià 7, 08029 Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Torrent
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellé s/n, 46100 Burjasot, Valencia, Spain. Electronic address: maria.j.alcaraz@uv.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000187:drug effects / Q000473:pathology*; D000070598:Anterior Cruciate Ligament Injuries / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D002809:Chondroitin Sulfates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005944:Glucosamine / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D020011:Protective Agents; D002809:Chondroitin Sulfates; D005944:Glucosamine
keywords: Anterior cruciate ligament transection model; Chondroitin sulfate-glucosamine; Osteoarthritis; Ovariectomised rats