PMID- 23776697
OWN - NLM
STAT- In-Process
DA  - 20130618
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 6
DP  - 2013
TI  - Acute-phase serum amyloid a in osteoarthritis: regulatory mechanism and
      proinflammatory properties.
PG  - e66769
LID - 10.1371/journal.pone.0066769 [doi]
AB  - 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-gamma agonists (genistein and rosiglitazone) and
      up-regulated by TGF-beta1 through Alk1 (Smad1/5) pathway. RhSAA induced
      proinflammatory cytokines (IL-6, IL-8, GRO-alpha 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.
FAU - de Seny, Dominique
AU  - de Seny D
AD  - Laboratory of Rheumatology, GIGA Research, University of Liege, CHU Liege, Liege,
      Belgium. ddeseny@chu.ulg.ac.be
FAU - Cobraiville, Gael
AU  - Cobraiville G
FAU - Charlier, Edith
AU  - Charlier E
FAU - Neuville, Sophie
AU  - Neuville S
FAU - Esser, Nathalie
AU  - Esser N
FAU - Malaise, Denis
AU  - Malaise D
FAU - Malaise, Olivier
AU  - Malaise O
FAU - Calvo, Florence Quesada
AU  - Calvo FQ
FAU - Relic, Biserka
AU  - Relic B
FAU - Malaise, Michel G
AU  - Malaise MG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130612
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
PMC - PMC3680431
OID - NLM: PMC3680431
EDAT- 2013/06/19 06:00
MHDA- 2013/06/19 06:00
CRDT- 2013/06/19 06:00
PHST- 2013 [ppublish]
PHST- 2013/03/20 [received]
PHST- 2013/05/11 [accepted]
PHST- 2013/06/12 [epublish]
AID - 10.1371/journal.pone.0066769 [doi]
AID - PONE-D-13-11865 [pii]
PST - epublish
SO  - PLoS One. 2013 Jun 12;8(6):e66769. doi: 10.1371/journal.pone.0066769. Print 2013.