title: Effects of BIS076 in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats.
abstract: BACKGROUND
  Osteoarthritis (OA) is the most frequent articular disease and a leading cause of disability. There is a need for effective treatments able to slow the progression of disease. Some of the available treatments are dietary supplements providing natural components. Recent studies have shown that estrogen deficiency contributes to the pathophysiological events of OA progression.
  
  
  METHODS
  We have used the anterior cruciate ligament transection model of OA in ovariectomised rats to study the effects of BIS076, a new formulation of a natural porcine cartilage extract associated with hydroxyapatite (as a source of calcium) and vitamin D3. Cartilage degradation, proteoglycan depletion and synovitis were followed by histochemistry. Effects on bone microstructure were determined by μCT. The levels of biomarkers in serum and inflammatory mediators in knee homogenates were measured by luminex or ELISA.
  
  
  RESULTS
  Oral administration of BIS076 reduced articular cartilage damage and serum levels of cartilage degradation markers C-telopeptide of type II collagen and cartilage oligomeric matrix protein, as well as matrix metalloproteinase-3. The local inflammatory response was down-regulated by BIS076 with lower production of pro-inflammatory cytokines and prostaglandin E2 in joint tissues. In addition, BIS076 was effective on metaphyseal bone alterations as this formulation increased volumetric bone mineral density and improved bone micro-architecture. These effects were related to the modification of bone metabolism reflected by changes in bone biomarkers with reductions in the ratio receptor activator of nuclear factor κB ligand/osteoprotegerin and the levels of tartrate-resistant acid phosphatase-5b, suggesting an inhibitory activity of BIS076 on trabecular bone resorption.
  
  
  CONCLUSIONS
  We have demonstrated the protective properties of a new formulation (BIS076) on joint lesion and bone alterations in an experimental model of OA in ovariectomised rats. This study supports the interest of BIS076 in OA treatments.
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain. luisa.ferrandiz@uv.es.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Ferrándiz
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain. carmen.terencio@uv.es.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Terencio
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain. carmen.carceller@gmail.com.
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. rruhi@bioiberica.com.
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. pdalmau@bioiberica.com.
authors.forename: Pere
authors.initials: P
authors.lastname: Dalmau
authors.affiliation: Pre-Clinical R&D Department, Pharmascience Div., BIOIBERICA S.A., Francesc Macià 7, 08029, Barcelona, Spain. jverges@bioiberica.com.
authors.forename: Josep
authors.initials: J
authors.lastname: Vergés
authors.affiliation: Pre-Clinical R&D Department, Pharmascience Div., BIOIBERICA S.A., Francesc Macià 7, 08029, Barcelona, Spain. lmontell@bioiberica.com.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Montell
authors.affiliation: Pre-Clinical R&D Department, Pharmascience Div., BIOIBERICA S.A., Francesc Macià 7, 08029, Barcelona, Spain. atorrent@bioiberica.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Torrent
authors.affiliation: Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain. maria.j.alcaraz@uv.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D015415:Biomarkers / Q000097:blood; D064236:Cartilage Oligomeric Matrix Protein / Q000097:blood; D024043:Collagen Type II / Q000097:blood / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D004195:Disease Models, Animal; D017886:Durapatite / Q000627:therapeutic use; D005260:Female; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020370:Osteoarthritis, Knee / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D010052:Ovariectomy / Q000009:adverse effects*; D010446:Peptide Fragments / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014020:Tissue Extracts / Q000627:therapeutic use*; D016896:Treatment Outcome; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; C000590554:C-terminal cross-linking telopeptide of type II collagen, human; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D016207:Cytokines; D006025:Glycosaminoglycans; D010446:Peptide Fragments; D014020:Tissue Extracts; D014807:Vitamin D; D017886:Durapatite; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone