The role of cyclooxygenase-2, interleukin-1β and fibroblast growth factor-2 in the activation of matrix metalloproteinase-1 in sheared-chondrocytes and articular cartilage.
The role of cyclooxygenase-2, interleukin-1β and fibroblast growth factor-2 in the activation of matrix metalloproteinase-1 in sheared-chondrocytes and articular cartilage.
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环氧化酶 2、白细胞介素 1 β 和成纤维细胞生长因子 2 在剪切软骨细胞和关节软骨中基质金属蛋白酶 1 激活中的作用
DOI：
10.1038/srep10412
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发表时间：
2015-05-20
影响因子：
4.6
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Guan PP;Guo JW;Yu X;Wang Y;Wang T;Konstantopoulos K;Wang ZY;Wang P
在流体剪应力(20 dyn/cm~2)激活和骨关节炎人软骨细胞中检测到基质金属蛋白酶-1的表达，然而，剪切诱导基质金属蛋白酶-1合成的确切机制尚不清楚。以原代软骨细胞和T/C-28a2软骨细胞为模型，我们报道了长时间高剪切作用于人软骨细胞诱导环氧合酶-2(COX-2)、白介素1-β(IL-1β)和成纤维细胞生长因子-2(FGF2)的合成，导致MMP1表达显著增加。IL-1β、COX-2依赖的前列腺素E_2激活PI3-K/AKT和p38信号通路，进而通过核因子-κB和c-jun反式激活途径合成基质金属蛋白酶-1。长时间剪应力暴露(>；12 h)可诱导15-脱氧前列腺素J2(15-deoxy-Δ12，14-prostaglandin J2，15d-PGJ2)合成。15d-PGJ2虽然抑制PI3-K/AKT和p38信号通路，但通过激活血红素加氧酶-1(HO-1)刺激基质金属蛋白酶-1的表达。COX-2+/−转基因小鼠在口服罗非昔布的情况下，证实了COX-2在体内调节关节软骨中基质金属蛋白酶-1表达的关键作用。这些发现为开发抗击骨性关节炎的治疗策略提供了新的见解。
MMP-1 expression is detected in fluid shear stress (20 dyn/cm2)-activated and osteoarthritic human chondrocytes, however, the precise mechanisms underlying shear-induced MMP-1 synthesis remain unknown. Using primary chondrocytes and T/C-28a2 chondrocytic cells as model systems, we report that prolonged application of high fluid shear to human chondrocytes induced the synthesis of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β) and fibroblast growth factor-2 (FGF-2), which led to a marked increase in MMP-1 expression. IL-1β, COX-2-dependent PGE2 activated the PI3-K/AKT and p38 signaling pathways, which were in turn responsible for MMP-1 synthesis via NF-κB- and c-Jun-transactivating pathways. Prolonged shear stress exposure (>12 h) induced 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) synthesis. Although 15d-PGJ2 suppressed PI3-K/AKT and p38 signaling pathways, it stimulated MMP-1 expression via activating heme oxygenase 1 (HO-1). The critical role of COX-2 in regulating MMP-1 expression in articular cartilage in vivo was demonstrated using COX-2+/− transgenic mice in the absence or presence of rofecoxib oral administration. These findings provide novel insights for developing therapeutic strategies to combat OA.
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影响因子：
3.7
作者：
Neeb L;Hellen P;Boehnke C;Hoffmann J;Schuh-Hofer S;Dirnagl U;Reuter U
通讯作者：
Reuter U
影响因子：
--
作者：
Akhtar N;Miller MJ;Haqqi TM
通讯作者：
Haqqi TM
影响因子：
10.8
作者：
Bond, M;Chase, AJ;Newby, AC
通讯作者：
Newby, AC
影响因子：
2.3
作者：
Kaspiris, A.;Khaldi, L.;Papadimitriou, E.
通讯作者：
Papadimitriou, E.
影响因子：
2.7
作者：
Honsawek, Sittisak;Yuktanandana, Pongsak;Parkpian, Vinai
通讯作者：
Parkpian, Vinai