Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis.

Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis.
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DOI:
10.1186/s12944-018-0864-8
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发表时间:
2018-09-11
影响因子:
4.5
通讯作者:
Takaso M
Takaso M
中科院分区:
医学3区
文献类型:
--
作者:
Aikawa J;Uchida K;Takano S;Inoue G;Iwase D;Miyagi M;Mukai M;Shoji S;Sekiguchi H;Takaso M

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髌下脂肪垫(IFP)与膝关节骨关节炎(KOA)有关。降钙素基因相关肽(CGRP)是一种在关节组织和滑膜组织(ST)中表达的血管活性神经肽,最近发现与KOA进展和疼痛相关。CGRP在人类KOA患者的IFPs中表达;然而,其调节尚未阐明。在全膝关节置换术(TKR)期间从138例KOA患者中采集IFP和ST,并使用实时聚合酶链反应(PCR)分析CGRP、环氧合酶-2(考克斯-2)和微粒体前列腺素E合酶-1(mPGES-1)表达。为了研究前列腺素E2(PGE 2)对CGRP的调节,使用胶原酶从IFPs中收获脂肪细胞(Ad)和基质血管组分(SVF)。还从ST收获滑膜细胞(SYC)并用媒介物(无血清培养基)、PGE 2或CGRP刺激。CGRP、考克斯-2和mPGES-1的表达水平在IFP中显著高于ST。前列腺素E2刺激增加CGRP的表达在Ad,SVF,SYC,然而,CGRP的表达显着高于PGE 2刺激的SVF比PGE 2刺激的SYC。CGRP刺激对考克斯-2或mPGES-1表达无影响。KOA患者IFP中CGRP的表达受考克斯-2/mPGES-1/PGE 2通路调节。
The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed in the IFPs of human KOA patients; however, its regulation has not been elucidated. IFPs and STs were harvested from 138 KOA patients during total knee replacement (TKR) and analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR). To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and the stromal vascular fraction (SVF) were harvested from IFPs using collagenase. Synovial cells (SYC) were also harvested from ST and stimulated with vehicle (serum-free culture medium), PGE2, or CGRP. CGRP, COX-2, and mPGES-1 expression levels were significantly higher in IFPs than STs. PGE2 stimulation increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP stimulation had no effect on COX-2 or mPGES-1 expression. CGRP expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2 pathway.
DOI: 10.2147/jpr.s135939
发表时间: 2017
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