Regulation of the inflammatory response by tin protoporphyrin IX in the rat anterior cruciate ligament transection model of osteoarthritis

• Published in: Journal of orthopaedic research 2011-09, Vol.29 (9), p.1375-1382
• Main Authors: Braza-Boïls, Aitana, Alcaraz, Maria José, Ferrándiz, Maria Luisa
• Format: Article
• Language: English
• Subjects: animal model; Animals; Anterior Cruciate Ligament - surgery; Anterior Cruciate Ligament Injuries; anterior cruciate ligament transection; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biomarkers; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cytokines - metabolism; Dinoprostone - metabolism; Disease Models, Animal; Enzyme Inhibitors - pharmacology; inflammation; Male; Metalloporphyrins - pharmacology; osteoarthritis; Osteoarthritis - drug therapy; Osteoarthritis - metabolism; Osteoarthritis - pathology; Protoporphyrins - pharmacology; Rats; Rats, Wistar; Stifle - drug effects; Stifle - metabolism; tin protoporphyrin IX
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1002/jor.21411

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 PGE2 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 PGE2 in serum and IL‐17 and PGE2 in ACLT knees. These effects on PGE2 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. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1375–1382, 2011