title: The impact of early intra-articular administration of interleukin-1 receptor antagonist on lubricin metabolism and cartilage degeneration in an anterior cruciate ligament transection model.
abstract: OBJECTIVE
  Study the impact of intra-articular interleukin-1 receptor antagonist (IL-1 ra) treatment on lubricin biosynthesis following anterior cruciate ligament transection (ACLT) in the rat and evaluate the effect of combined IL-1 ra and recombinant human lubricin (rhPRG4) treatments on chondrocyte apoptosis.
  
  
  METHODS
  ACLT was performed in male Lewis rats. Treatments included IL-1 ra or vehicle (n = 36 in each group). IL-1 ra intra-articular dosing was performed on days 1, 3, 5 and 7 following ACLT using Anakinra (150 mg/ml; 40 μl). At 3 and 5 weeks, animals were sacrificed and RNA was isolated. Histological analyses included Safranin O and H&E. Lubricin synovial fluid (SF) lavage concentrations were determined at 5 weeks. ACLT animals were treated with a single injection of vehicle, IL-1 ra (75 mg/ml; 40 μl), rhPRG4 (200 μg/ml; 40 μl), or IL-1 ra + rhPRG4 (75 mg/ml + 200 μg/ml; 40 μl) (n = 6 in each group) on day 7 following ACLT and cartilage was probed for cleaved caspase-3 at 5 weeks.
  
  
  RESULTS
  IL-1 ra treatment improved lubricin expression (P < 0.001) and lubricin SF lavage concentrations in the IL-1 ra group was higher (P = 0.005) than the vehicle. IL-1 ra treatment reduced cartilage and synovial scores (P < 0.001) compared to vehicle. IL-1 ra and rhPRG4 acted synergistically to reduce caspase-3 positive chondrocytes (P < 0.001) compared to individual treatments.
  
  
  CONCLUSIONS
  IL-1 ra treatment preserved lubricin following ACLT and a combined treatment of IL-1 ra + rhPRG4 may act synergistically to reduce cartilage catabolism.
authors.affiliation: Department of Pharmaceutical Sciences, MCPHS University, Boston, MA 02115, USA. Electronic address: Khaled.elsaid@mcphs.edu.
authors.forename: K A
authors.initials: KA
authors.lastname: Elsaid
authors.affiliation: Department of Emergency Medicine, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, MCPHS University, Boston, MA 02115, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Shaman
authors.affiliation: Department of Pharmaceutical Sciences, MCPHS University, Boston, MA 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Patel
authors.affiliation: Faculty of Kinesiology and Schulich School of Engineering, University of Calgary, Canada.
authors.forename: T A
authors.initials: TA
authors.lastname: Schmidt
authors.affiliation: Department of Emergency Medicine, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Jay
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000378:metabolism* / Q000601:surgery*; D017209:Apoptosis; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D007270:Injections, Intra-Articular; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D008297:Male; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013997:Time Factors; D000099158:Proteoglycan 4
chemical_list: D006023:Glycoproteins; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D000099158:Proteoglycan 4
keywords: Interleukin-1 receptor antagonist; Lubricin; Posttraumatic osteoarthritis