title: Regulation of the inflammatory response by tin protoporphyrin IX in the rat anterior cruciate ligament transection model of osteoarthritis.
abstract: The purpose of this study was to investigate several inflammatory mediators and cartilage degradation molecules as possible biomarkers of joint lesion in the anterior cruciate ligament transection (ACLT) model of osteoarthritis in rats. We also assessed whether the treatment with the anti-inflammatory agent tin protoporphyrin IX (SnPP) reduces the progression of disease. Our results indicate that serum levels of interleukin (IL)-6 and PGE(2) are significantly increased in ACLT rats 10 weeks after surgery, whereas the increases in IL-1β and tumor necrosis-α were not significant. In addition, our data suggest that IL-17 is the main pro-inflammatory cytokine in the ACLT joint. We have shown that serum C-telopeptide of type II collagen (CTX-II) is a biomarker better than cartilage oligomeric matrix protein, whereas hyaluronic acid showed no correlation with disease progression. Administration of SnPP (i.p. 12 mg/kg BW/day for 10 weeks) reduces the severity of structural changes and the levels of CTX-II, IL-6, and PGE(2) in serum and IL-17 and PGE(2) in ACLT knees. These effects on PGE(2) are dependent on the down-regulation of cyclooxygenase-2. Our findings indicate that systemic and local inflammatory mediators participate in the rat ACLT model and anti-inflammatory strategies may help to reduce the progression of joint lesion.
authors: Department of Pharmacology, University of Valencia, and IDM, Valencia, Spain.
authors: Aitana
authors: A
authors: Braza-Boïls
authors: Maria José
authors: MJ
authors: Alcaraz
authors: Maria Luisa
authors: ML
authors: Ferrándiz
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D000070598:Anterior Cruciate Ligament Injuries; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015415:Biomarkers; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013264:Stifle / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016207:Cytokines; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D015232:Dinoprostone