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

Abstract

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.

• Authors: S C M van Dalen, A B Blom, A W Slöetjes, M M A Helsen, J Roth, T Vogl, F A J van de Loo, M I Koenders, P M van der Kraan, W B van den Berg, M H J van den Bosch, P L E M van Lent
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 25 Issue 3 Pg. 385-396 (03 2017) ISSN: 1522-9653 [Electronic] England
• PMID: 27654963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Interleukin-1
• Interleukin-1alpha
• Interleukin-1beta
• Collagenases

Topics

• Animals
• Cartilage (pathology)
• Collagenases (metabolism)
• Female
• Interleukin-1 (metabolism)
• Interleukin-1alpha (metabolism)
• Interleukin-1beta (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Osteoarthritis (etiology, metabolism, pathology)
• Real-Time Polymerase Chain Reaction
• Synovial Membrane (metabolism)
• Synovitis (etiology, metabolism, pathology)
• Transcriptome