Increase and regulation of synovial calcitonin gene-related peptide expression in patients with painful knee osteoarthritis.
Increase and regulation of synovial calcitonin gene-related peptide expression in patients with painful knee osteoarthritis.
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DOI：
10.2147/jpr.s135939
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发表时间：
2017
影响因子：
2.7
通讯作者：
Takaso M
中科院分区：
文献类型：
--
作者：
Takano S;Uchida K;Inoue G;Minatani A;Miyagi M;Aikawa J;Iwase D;Onuma K;Mukai M;Takaso M
最近的研究表明，血管舒张神经肽降钙素基因相关肽（CGRP）定位于滑膜组织，并可能参与髋关节和膝关节骨关节炎（OA）的病理。然而，人类OA患者滑膜组织中疼痛与CGRP表达水平之间的调节和关系尚不完全清楚。在全膝关节置换术期间，从74名膝关节OA患者（单侧kelgren /Lawrence分级3-4级）身上采集滑膜组织。采用免疫组化方法对切除组织中表达cgrp的细胞进行鉴定。为了检测CGRP的表达水平，我们从滑膜组织中分离出CD14阳性（CD14+）（富含巨噬细胞的细胞部分）和CD14阴性（CD14−；富含成纤维细胞的细胞部分）细胞。为了研究前列腺素E2 （PGE2）在调节CGRP表达中的作用，我们用PGE2刺激培养的CD14−和CD14+细胞。此外，比较强/重度（视觉模拟评分[VAS]≥6）和轻/中度疼痛（VAS<6） OA患者滑膜组织中CGRP的表达水平。cgrp阳性细胞见于内膜层，包括CD14−细胞和CD14+细胞。CGRP在非培养CD14−组中的表达明显高于CD14+组。与未处理的CD14 -细胞组分相比，外源性PGE2处理的CD14 -细胞组分中CGRP的表达水平显著增加。相比之下，无论CD14+细胞是否表达CGRP， PGE2治疗都不会增加CGRP。此外，VAS≥6组的CGRP表达也显著高于VAS<6组。这些发现提示滑膜成纤维细胞中的CGRP表达受COX-2/PGE2通路的调控，滑膜CGRP水平升高可能导致OA疼痛。
Recent studies suggest that the vasodilatory neuropeptide calcitonin gene-related peptide (CGRP) is localized in the synovial tissue and may be involved in the pathology of hip and knee osteoarthritis (OA). However, the regulation and relationship between pain and CGRP expression levels in the synovial tissue of human OA patients are not fully understood. Synovial tissues were harvested from 74 participants with radiographic knee OA (unilateral Kellgren/Lawrence grades 3–4) during total knee arthroplasty. CGRP-expressing cells in the resected tissue were identified by immunohistochemical analyses. To examine CGRP expression levels, CD14-positive (CD14+) (macrophage-rich cell fraction) and CD14-negative (CD14−; fibroblast-rich cell fraction) cells were isolated from the synovial tissue. To investigate the involvement of prostaglandin E2 (PGE2) in the regulation of CGRP expression, cultured CD14− and CD14+ cells were stimulated with PGE2. In addition, CGRP expression levels in the synovial tissue of OA patients with strong/severe (visual analog scale [VAS]≥6) and mild/moderate pain (VAS<6) were compared. CGRP-positive cells were detected in the intimal lining layer and comprised both CD14− and CD14+ cells. CGRP expression in non-cultured CD14− fractions was significantly higher than that in CD14+ fractions. The expression levels of CGRP were significantly increased in cultured CD14− cell fractions treated with exogenous PGE2, compared to untreated CD14− cell fractions. In contrast, treatment with PGE2 did not increase CGRP regardless of whether or not CD14+ cells expressed CGRP. Furthermore, CGRP expression in the VAS≥6 group was also significantly higher than that in the VAS<6 group. These findings suggest that CGRP expression in the synovial fibroblasts is regulated by the COX-2/PGE2 pathway and that elevation of synovial CGRP levels may contribute to OA pain.