Details

Autor(en) / Beteiligte

• van Dalen, S.C.M
• Blom, A.B
• Slöetjes, A.W
• Helsen, M.M.A
• Roth, J
• Vogl, T
• van de Loo, F.A.J
• Koenders, M.I
• van der Kraan, P.M
• van den Berg, W.B
• van den Bosch, M.H.J
• van Lent, P.L.E.M

Titel

Interleukin-1 is not involved in synovial inflammation and cartilage destruction in collagenase-induced osteoarthritis

Ist Teil von

• Osteoarthritis and cartilage, 2017-03, Vol.25 (3), p.385-396

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary Objective 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). Methods 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). Results 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. Conclusions 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.