Dataset Information
Acute-phase serum amyloid a in osteoarthritis: regulatory mechanism and proinflammatory properties.
Ontology highlight
ABSTRACT: Objective
To determine if serum amyloid A (A-SAA) could be detected in human osteoarthritic (OA) joints and further clarify if high A-SAA level in joints result from a local production or from a diffusion process from abnormally elevated plasma concentration. Regulatory mechanism of A-SAA expression and its pro-inflammatory properties were also investigated.Methods
A-SAA levels in serum and synovial fluid of OA (n?=?29) and rheumatoid arthritis (RA) (n?=?27) patients were measured and compared to matched-healthy volunteers (HV) (n?=?35). In vitro cell cultures were performed on primary joint cells provided from osteoarthritis patients. Regulatory mechanisms were studied using Western-blotting, ELISA and lentiviral transfections.Results
A-SAA was statistically increased in OA plasma patients compared to HV. Moreover, A-SAA level in OA plasma and synovial fluid increased with the Kellgren & Lauwrence grade. For all OA and RA patients, A-SAA plasma level was higher and highly correlated with its corresponding level in the synovial fluid, therefore supporting that A-SAA was mainly due to the passive diffusion process from blood into the joint cavity. However, A-SAA expression was also observed in vitro under corticosteroid treatment and/or under IL-1beta stimuli. A-SAA expression was down-regulated by PPAR-? agonists (genistein and rosiglitazone) and up-regulated by TGF-?1 through Alk1 (Smad1/5) pathway. RhSAA induced proinflammatory cytokines (IL-6, IL-8, GRO-? and MCP-1) and metalloproteinases (MMP-1, MMP-3 and MMP-13) expression in FLS and chondrocytes, which expression was downregulated by TAK242, a specific TLR4 inhibitor.Conclusion
Systemic or local A-SAA expression inside OA joint cavity may play a key role in inflammatory process seen in osteoarthritis, which could be counteracted by TLR4 inhibition.
SUBMITTER: de Seny D
PROVIDER: S-EPMC3680431 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Publications
Acute-phase serum amyloid a in osteoarthritis: regulatory mechanism and proinflammatory properties.
PloS one 20130612 6
<h4>Objective</h4>To determine if serum amyloid A (A-SAA) could be detected in human osteoarthritic (OA) joints and further clarify if high A-SAA level in joints result from a local production or from a diffusion process from abnormally elevated plasma concentration. Regulatory mechanism of A-SAA expression and its pro-inflammatory properties were also investigated.<h4>Methods</h4>A-SAA levels in serum and synovial fluid of OA (n = 29) and rheumatoid arthritis (RA) (n = 27) patients were measure ...[more]