Increasing expression of substance P and calcitonin gene-related peptide in synovial tissue and fluid contribute to the progress of arthritis in developmental dysplasia of the hip.
Increasing expression of substance P and calcitonin gene-related peptide in synovial tissue and fluid contribute to the progress of arthritis in developmental dysplasia of the hip.
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滑膜组织和液体中P物质和降钙素基因相关肽的表达增加有助于髋关节发育不良中关节炎的进展。
DOI：
10.1186/s13075-014-0513-1
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发表时间：
2015-01-12
影响因子：
4.9
通讯作者：
Chen XD
中科院分区：
文献类型：
--
作者：
Wang H;Zhang X;He JY;Zheng XF;Li D;Li Z;Zhu JF;Shen C;Cai GQ;Chen XD
发育性髋关节发育不良（DDH）是一种常见的肌肉骨骼疾病，其主要病理特征为疼痛和关节功能丧失。本研究探讨了P物质（SP）和降钙素基因相关肽（CGRP）在DDH关节炎病理和炎症过程中的可能参与和调节机制。采集不同程度DDH患者和股骨颈骨折患者的血液、滑膜组织和液体样本。采用免疫组化、实时荧光定量PCR和酶联免疫吸附试验（ELISA）检测各组大鼠滑膜和滑液中SP、CGRP和炎性细胞因子的含量。用偏相关分析评价SF中神经肽和炎性细胞因子的相关性。采用实时荧光定量PCR和酶联免疫吸附试验（ELISA）检测SP和CGRP对中度DDH患者滑膜细胞的促炎作用。通过Western blot分析和活化B细胞核因子κ轻链增强子（NF-κB）DNA结合试验，探讨其作用机制。与中度DDH和对照组相比，在重度DDH组患者的滑膜和SF中观察到神经肽和炎性细胞因子的水平显著增加。在中度DDH样本中，SF中的SP与肿瘤坏死因子（TNF）-α相关，SF中的CGRP与TNF-α和白细胞介素（IL）-10相关。重度DDH组SF中SP与IL-1 β、TNF-α、IL-10相关。SF中CGRP与TNF-α相关。此外，SP可能通过激活NF-κB对滑膜细胞有明显的促炎作用。滑膜和SF中SP和CGRP的表达上调可能参与了DDH关节炎的炎症过程。NF-κB通路的激活在SP对滑膜细胞的促炎作用中是不可或缺的。这一原始发现可能表明DDH的潜在临床药物靶点和创新疗法的发展。
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder that has pain and loss of joint function as major pathological features. In the present study, we explored the mechanisms of possible involvement and regulation of substance P (SP) and calcitonin gene-related peptide (CGRP) in the pathological and inflammatory processes of arthritis in DDH. Blood, synovial tissue and fluid samples were collected from patients diagnosed with different severities of DDH and from patients with femoral neck fracture. Levels of SP, CGRP and inflammatory cytokines in synovium and synovial fluid (SF) in the different groups were evaluated by immunohistochemistry, real-time PCR and enzyme-linked immunosorbent assay (ELISA). Correlations between neuropeptides and inflammatory cytokines in SF were evaluated by partial correlation analysis. The proinflammatory effects of SP and CGRP on synoviocytes obtained from patients with moderate DDH were investigated in vitro by real-time PCR and ELISA. The mechanisms of those effects were evaluated by Western blot analysis and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) DNA binding assay. Significantly increased levels of neuropeptides and inflammatory cytokines were observed in synovium and SF from patients in the severe DDH group compared with the moderate DDH and control groups. In moderate DDH samples, SP in SF correlated with tumor necrosis factor (TNF)-α, and CGRP in SF correlated with TNF-α and interleukin (IL)-10. In the severe DDH group, SP in SF correlated with interleukin (IL)-1β, TNF-α and IL-10. CGRP in SF correlated with TNF-α. Additionally, SP might have had obvious proinflammatory effects on synoviocytes through the activation of NF-κB. The upregulation of SP and CGRP in synovium and SF might participate in the inflammatory process of arthritis in DDH. The activation of the NF-κB pathway seems indispensable in the proinflammatory effect of SP on synoviocytes. This original discovery may indicate a potential clinical drug target and the development of innovative therapies for DDH.
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影响因子：
2.2
作者：
Nakamura, Junichi;Oinuma, Kazuhiro;Kishida, Shunji
通讯作者：
Kishida, Shunji
影响因子：
1.7
作者：
Miura, Yoko;Ohtori, Seiji;Takahashi, Kazuhisa
通讯作者：
Takahashi, Kazuhisa
DOI：
10.1016/j.bbrc.2014.09.090
发表时间：
2014-10-10
影响因子：
3.1
作者：
Hong, Hyun Sook;Son, Youngsook
通讯作者：
Son, Youngsook
影响因子：
4
作者：
Bentz, Mireille;Zaouter, Charlotte;Benderdour, Mohamed
通讯作者：
Benderdour, Mohamed
关节炎严重性基因座CIA5D是滑膜成纤维细胞侵入性特性的新型遗传调节剂。
影响因子：
--
作者：
Laragione, Teresina;Brenner, Max;Mello, Adriana;Symons, Marc;Gulko, Percio S.
通讯作者：
Gulko, Percio S.