Abstract | BACKGROUND: Soluble biglycan (sBGN) and soluble decorin (sDCN), are two closely related essential components of extracellular matrix which both have been shown to possess proinflammatory properties. We studied whether sBGN or sDCN were present in synovial fluid (SF) of osteoarthritis (OA) or rheumatoid arthritis (RA) patients and studied sBGN or sDCN potential role in the degradation of OA cartilage. METHODS: RESULTS: sBGN was found in meniscus tear SF (14 ± 2 ng/ml), OA SF (582 ± 307 ng/ml) and RA SF (1191 ± 482 ng/ml). Low levels of sDCN could also be detected in SF of meniscus tear (51 ± 4) ng/ml, OA (52 ± 3 ng/ml), and RA (49 ± 4 ng/ml). Stimulation of chondrocytes with sBGN increased significantly the mRNA and protein expression of catabolic MMPs, including MMP1, MMP9 and MMP13, and of inflammatory cytokines interleukin (IL)-6 and IL-8, whereas the expression of anabolic markers aggrecan and collagen type II was decreased. sBGN induced release of proteoglycans, collagen and NO from chondrocytes and cartilage explants. The catabolic response in explants was dependent of OA cartilage degradation stage. The mechanism of action of sBGN was mainly mediated through the TLR4-nuclear factor-κB pathway. CONCLUSIONS: High levels of sBGN was found in advanced OA and RA SF. sBGN activates chondrocytes mainly via TLR4, which results in net loss of cartilage. Thus, sBGN can be a mediator of OA cartilage degradation and also a potential biomarker for arthritis.
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Authors | Goncalo Barreto, Antti Soininen, Pekka Ylinen, Jerker Sandelin, Yrjö T Konttinen, Dan C Nordström, Kari K Eklund |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 17
Pg. 379
(Dec 24 2015)
ISSN: 1478-6362 [Electronic] England |
PMID | 26703441
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BGN protein, human
- Biglycan
- Biomarkers
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Topics |
- Aged
- Arthritis, Rheumatoid
(metabolism)
- Biglycan
(metabolism)
- Biomarkers
(analysis)
- Cartilage, Articular
(immunology, metabolism, pathology)
- Enzyme-Linked Immunosorbent Assay
- Female
- HEK293 Cells
- Humans
- Male
- Middle Aged
- Osteoarthritis, Knee
(immunology, metabolism, pathology)
- Real-Time Polymerase Chain Reaction
- Synovial Fluid
(chemistry, immunology, metabolism)
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