title: Interleukin-1 is not involved in synovial inflammation and cartilage destruction in collagenase-induced osteoarthritis.
abstract: Interleukin-1 (IL-1) is an alleged important cytokine in osteoarthritis (OA), although the exact contribution of IL-1 to joint destruction remains unclear. Here we investigated the involvement of IL-1α and IL-1β in joint pathology during collagenase-induced OA (CiOA).
  
  
  
  CiOA was induced in wild type (WT) and IL-1αβ-/-mice. Additionally, IL-1 signaling was inhibited in WT mice with CiOA using osmotic pumps containing IL-1RA. Joint pathology was assessed using histology. Activity of cartilage-degrading enzymes was determined using antibodies against aggrecan neo-epitopes VDIPEN and NITEGE. Synovial gene expression was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Serum protein levels were measured with Luminex or enzyme-linked immunosorbent assay (ELISA).
  
  
  
  Synovial IL-1β expression was strongly elevated 7 days after induction of CiOA in WT mice but decreased afterwards, whereas S100A8/A9, previously described to aggravate OA, remained elevated for 21 days. Remarkably, synovial inflammation was comparable between WT and IL-1αβ-/-mice on day 7 of CiOA. In line, synovial mRNA expression of genes involved in IL-1 signaling and inflammatory mediators was comparable between WT and IL-1αβ-/-mice, and serum levels for Keratinocyte Chemoattractant (KC)/IL-6/S100A8/S100A9/IL-10 were equal. Synovial matrix metalloproteinase (MMP)/aggrecanase expression and activity in cartilage was not different in WT and IL-1αβ-/-mice on day 7 of CiOA. Cartilage destruction on day 42 was not different between WT and IL-1αβ-/-mice, which was supported by our finding that IL-1RA treatment in WT mice with CiOA did not alter joint destruction.
  
  
  
  IL-1α and IL-1β are not involved in synovial inflammation and cartilage destruction during CiOA, implicating that other mediators are responsible for the joint damage.
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Stephanie.vanDalen@radboudumc.nl.
authors.forename: S C M
authors.initials: SC
authors.lastname: van Dalen
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Arjen.Blom@radboudumc.nl.
authors.forename: A B
authors.initials: AB
authors.lastname: Blom
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Annet.Sloetjes@radboudumc.nl.
authors.forename: A W
authors.initials: AW
authors.lastname: Slöetjes
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Monique.Helsen@radboudumc.nl.
authors.forename: M M A
authors.initials: MM
authors.lastname: Helsen
authors.affiliation: Institute of Immunology, University of Münster, Münster, Germany. Electronic address: rothj@uni-muenster.de.
authors.forename: J
authors.initials: J
authors.lastname: Roth
authors.affiliation: Institute of Immunology, University of Münster, Münster, Germany. Electronic address: vogl@uni-muenster.de.
authors.forename: T
authors.initials: T
authors.lastname: Vogl
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Fons.vandeLoo@radboudumc.nl.
authors.forename: F A J
authors.initials: FA
authors.lastname: van de Loo
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Marije.Koenders@radboudumc.nl.
authors.forename: M I
authors.initials: MI
authors.lastname: Koenders
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Peter.vanderKraan@radboudumc.nl.
authors.forename: P M
authors.initials: PM
authors.lastname: van der Kraan
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Wim.vandenBerg@radboudumc.nl.
authors.forename: W B
authors.initials: WB
authors.lastname: van den Berg
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Martijn.vandenBosch@radboudumc.nl.
authors.forename: M H J
authors.initials: MH
authors.lastname: van den Bosch
authors.affiliation: Experimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Peter.vanLent@radboudumc.nl.
authors.forename: P L E M
authors.initials: PL
authors.lastname: van Lent
mesh_terms: D000818:Animals; D002356:Cartilage / Q000473:pathology*; D017364:Collagenases / Q000378:metabolism*; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism; D013585:Synovitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome
chemical_list: D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017364:Collagenases
keywords: Animal models; Cartilage destruction; Experimental OA; Interleukin-1; Osteoarthritis; Synovitis