Acute-phase serum amyloid a in osteoarthritis: regulatory mechanism and proinflammatory properties.
Acute-phase serum amyloid a in osteoarthritis: regulatory mechanism and proinflammatory properties.
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DOI：
10.1371/journal.pone.0066769
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Malaise MG
中科院分区：
文献类型：
--
作者：
de Seny D;Cobraiville G;Charlier E;Neuville S;Esser N;Malaise D;Malaise O;Calvo FQ;Relic B;Malaise MG
确定是否可以在人骨关节炎 (OA) 关节中检测到血清淀粉样蛋白 A (A-SAA)，并进一步阐明关节中高 A-SAA 水平是由局部产生还是由血浆浓度异常升高的扩散过程引起。还研究了 A-SAA 表达的调节机制及其促炎特性。测量 OA (n = 29) 和类风湿关节炎 (RA) (n = 27) 患者血清和滑液中的 A-SAA 水平，并与匹配的健康志愿者 (HV) (n = 35) 进行比较。对骨关节炎患者提供的原代关节细胞进行体外细胞培养。使用蛋白质印迹、ELISA 和慢病毒转染研究了调控机制。与 HV 患者相比，OA 血浆患者的 A-SAA 显着增加。此外，OA 血浆和滑液中的 A-SAA 水平随着 Kellgren & Lauwrence 分级的增加而增加。对于所有OA和RA患者，A-SAA血浆水平较高，并且与其在滑液中的相应水平高度相关，因此支持A-SAA主要是由于从血液到关节腔的被动扩散过程所致。然而，在体外皮质类固醇治疗和/或 IL-1β 刺激下也观察到 A-SAA 表达。 A-SAA 表达通过 Alk1 (Smad1/5) 途径被 PPAR-γ 激动剂（金雀异黄素和罗格列酮）下调，并被 TGF-β1 上调。 RhSAA 诱导 FLS 和软骨细胞中促炎细胞因子（IL-6、IL-8、GRO-α 和 MCP-1）和金属蛋白酶（MMP-1、MMP-3 和 MMP-13）的表达，而这种表达可被 TLR4 特异性抑制剂 TAK242 下调。 OA 关节腔内的全身或局部 A-SAA 表达可能在骨关节炎的炎症过程中发挥关键作用，可通过 TLR4 抑制来抵消。
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. 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. 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-γ agonists (genistein and rosiglitazone) and up-regulated by TGF-β1 through Alk1 (Smad1/5) pathway. RhSAA induced proinflammatory cytokines (IL-6, IL-8, GRO-α 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. 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.
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影响因子：
4.4
作者：
Connolly, Mary;Marrelli, Alessandra;Fearon, Ursula
通讯作者：
Fearon, Ursula
影响因子：
27.4
作者：
Conde, Javier;Gomez, Rodolfo;Gualillo, Oreste
通讯作者：
Gualillo, Oreste
影响因子：
64.5
作者：
BENYA, PD;PADILLA, SR;NIMNI, ME
通讯作者：
NIMNI, ME
DOI：
10.1111/j.1749-6632.1982.tb22124.x
发表时间：
1982-01-01
影响因子：
5.2
作者：
KUSHNER, I
通讯作者：
KUSHNER, I
尖端：TLR2是急性阶段血清淀粉样蛋白A的功能受体。
DOI：
10.4049/jimmunol.181.1.22
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cheng N;He R;Tian J;Ye PP;Ye RD
通讯作者：
Ye RD