Abstract | OBJECTIVE: METHODS: RESULTS: Immunisation of S100A9-/- mice with the antigen mBSA induced normal cellular and humoral responses, not different from wild type (WT) controls. However, joint swelling measured at day 3 and 7 after AIA induction was significantly lower (36 and 70%, respectively). Histologically, at day 7 AIA, cellular mass was much lower (63-80%) and proteoglycan depletion from cartilage layers was significantly reduced (between 50-95%). Cartilage destruction mediated by MMPs was absent in S100A9-/- mice but clearly present in controls. MMP3, 9 and 13 mRNA levels were significantly lowered in arthritic synovia of S100A9-/-. In vitro stimulation of macrophages by the heterodimer S100A8/A9 or S100A8 elevated mRNA levels of MMP3, 9 and in particular MMP13. Intra-articular injection of S100A8 caused prominent joint inflammation and depletion of proteoglycans at day 1. Significant upregulation of mRNA levels of S100A8/A9, cytokines ( interleukin 1 (IL1)), MMPs (MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4) was found in the synovium and correlated with strong upregulation of NITEGE neoepitopes within the cartilage layers. CONCLUSIONS:
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Authors | P L E M van Lent, L Grevers, A B Blom, A Sloetjes, J S Mort, T Vogl, W Nacken, W B van den Berg, J Roth |
Journal | Annals of the rheumatic diseases
(Ann Rheum Dis)
Vol. 67
Issue 12
Pg. 1750-8
(Dec 2008)
ISSN: 1468-2060 [Electronic] England |
PMID | 18055478
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calgranulin A
- Calgranulin B
- Cytokines
- Immunoglobulin G
- Proteoglycans
- RNA, Messenger
- S100 Proteins
- S100a8 protein, mouse
- methylated bovine serum albumin
- Serum Albumin, Bovine
- ADAM Proteins
- Matrix Metalloproteinases
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Topics |
- ADAM Proteins
(metabolism)
- Animals
- Arthritis, Experimental
(immunology, pathology)
- Calgranulin A
- Calgranulin B
(immunology)
- Cartilage, Articular
(pathology)
- Cell Death
- Chondrocytes
(pathology)
- Cytokines
(biosynthesis, genetics)
- Immunity, Cellular
- Immunoglobulin G
(biosynthesis)
- Macrophages, Peritoneal
(metabolism)
- Matrix Metalloproteinases
(metabolism)
- Mice
- Mice, Knockout
- Proteoglycans
(metabolism)
- RNA, Messenger
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
- S100 Proteins
(immunology)
- Serum Albumin, Bovine
(immunology)
- Synovial Membrane
(metabolism)
- Up-Regulation
(drug effects)
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