Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1/EP2/EP4 receptor pathway in synovium of knee osteoarthritis patients.
Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1/EP2/EP4 receptor pathway in synovium of knee osteoarthritis patients.
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DOI：
10.1186/s13018-016-0460-4
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发表时间：
2016-10-17
影响因子：
2.6
通讯作者：
Takaso M
中科院分区：
文献类型：
--
作者：
Minatani A;Uchida K;Inoue G;Takano S;Aikawa J;Miyagi M;Fujimaki H;Iwase D;Onuma K;Matsumoto T;Takaso M
降钙素基因相关肽(CGRP)是一种由37个氨基酸组成的扩血管神经肽，与受体活性修饰蛋白1(RAMP1)和降钙素受体样受体(CLR)结合。临床和临床前证据表明，CGRP与髋关节和膝关节疼痛有关，但滑膜组织中CGRP/CGRP受体信号的调节机制尚不完全清楚。43例膝关节骨关节炎(OA，单侧Kellgren/Lawrence(K/L)分级3~4级)患者在全膝关节置换术中采集滑膜组织。用实时定量聚合酶链式反应分析滑膜组织中降钙素基因相关肽与肿瘤坏死因子-α、白介素1、白介素6、环氧合酶-2(COX-2)β表达的相关性。为探讨降钙素基因相关肽及其受体表达的调控因素，用肿瘤坏死因子α、白介素1β、白介素6和前列腺素E_2刺激培养的滑膜细胞，并用前列腺素E_2受体激动剂处理。CGRP和COX-2定位于滑膜衬里。OA患者滑膜组织中COX-2的表达与CGRP的表达呈正相关。与未处理的对照细胞相比，经PGE2外源性处理的滑膜细胞中CGRP和RAMP1的基因表达显著增加。在培养的滑膜细胞中，EP4激动剂处理后CGRP基因表达显著增加，而外源性EP1和EP2激动剂处理后RAMP1基因表达显著增加。PGE2似乎通过EP受体调节膝骨性关节炎患者滑膜中的CGRP/CGRP受体信号。
Calcitonin gene-related peptide (CGRP) is a 37-amino-acid vasodilatory neuropeptide that binds to receptor activity-modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CLR). Clinical and preclinical evidence suggests that CGRP is associated with hip and knee joint pain; however, the regulation mechanisms of CGRP/CGRP receptor signaling in synovial tissue are not fully understood. Synovial tissues were harvested from 43 participants with radiographic knee osteoarthritis (OA; unilateral Kellgren/Lawrence (K/L) grades 3–4) during total knee arthroplasty. Correlationships between the mRNA expression levels of CGRP and those of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cycloxygenase-2 (COX-2) were evaluated using real-time PCR analysis of total RNA extracted from the collected synovial tissues. To investigate the factors controlling the regulation of CGRP and CGRP receptor expression, cultured synovial cells were stimulated with TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2) and were also treated with PGE2 receptor (EP) agonist. CGRP and COX-2 localized in the synovial lining layer. Expression of COX-2 positively correlated with CGRP mRNA expression in the synovial tissue of OA patients. The gene expression of CGRP and RAMP1 increased significantly in synovial cells exogenously treated with PGE2 compared to untreated control cells. In cultured synovial cells, CGRP gene expression increased significantly following EP4 agonist treatment, whereas RAMP1 gene expression increased significantly in the presence of exogenously added EP1 and EP2 agonists. PGE2 appears to regulate CGRP/CGRP receptor signaling through the EP receptor in the synovium of knee OA patients.
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DOI：
10.1124/jpet.106.105569
发表时间：
2006-12-01
影响因子：
3.5
作者：
Lin, Chung-Ren;Amaya, Fumimasa;Woolf, Clifford J.
通讯作者：
Woolf, Clifford J.
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：
7
作者：
Benschop, R. J.;Collins, E. C.;Chambers, M. G.
通讯作者：
Chambers, M. G.
影响因子：
3.6
作者：
Saxler, Guido;Loeer, Franz;Hanesch, Ulrike
通讯作者：
Hanesch, Ulrike
影响因子：
6.4
作者：
Ma, Weiya;Dumont, Yvan;Quirion, Remi
通讯作者：
Quirion, Remi