Increased synovial expression of calcitonin gene-related peptide and its potential roles in Charcot Neuroarthropathy

IF 2.8 4区医学 Q2 PATHOLOGY Experimental and molecular pathology Pub Date : 2022-10-01 DOI:10.1016/j.yexmp.2022.104835

Yi Guo , Lew Schon , Sharada Paudel , Tyler Feltham , Lumanti Manandhar , Zijun Zhang

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Abstract

Objective

Joint destruction in Charcot neuroarthropathy (CNA) is accompanied with abundant hyperplastic synovium. This study aimed to characterize the expression patterns of a group of neuropeptides in the CNA synovium.

Methods

Synovial specimens were collected during surgery from the CNA (n = 6) and non-CNA joints (n = 14). Tissue samples were processed for protein extraction and western blot for vasoactive intestinal peptide (VIP), galanin, and calcitonin gene-related peptide (CGRP). Immunohistochemistry was performed to localize CGRP in the CNA synovium. Additionally, CGRP was applied to fibroblast-like synoviocytes (FLS) isolated from CNA synovium for its effects on cell proliferation and collagenolysis in vitro.

Results

Western blot detected light bands of VIP in the CNA samples but abundant galanin in both CNA and non-CNA samples. Most of the CNA samples (5/6) increased expression of CGRP, with an average band density about 2 times that in the non-CNA group (p < .05). Immunohistochemistry of CGRP demonstrated intense staining in the intimal layer of the CNA synovium. In tissue culture, adding CGRP (10 nM) in the medium promoted FLS proliferation. In combination with TNF-α, CGRP enhanced FLS-mediated collagenolysis in vitro.

Conclusion

This study revealed an increased expression of CGRP in the CNA synovium and demonstrated that CGRP regulates FLS proliferation and collagenolytic activity, suggesting CGRP may contribute to the bone and cartilage destruction in CNA.

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滑膜降钙素基因相关肽表达的增加及其在Charcot神经关节病中的潜在作用

目的Charcot神经关节病(CNA)的关节破坏伴大量滑膜增生。本研究旨在描述一组神经肽在CNA滑膜中的表达模式。方法术中采集CNA关节(n = 6)和非CNA关节(n = 14)的滑膜标本。组织样品进行蛋白质提取和免疫印迹检测血管活性肠肽(VIP)、甘丙肽和降钙素基因相关肽(CGRP)。应用免疫组化方法定位CNA滑膜中的CGRP。此外，将CGRP应用于从CNA滑膜分离的成纤维细胞样滑膜细胞(FLS)，观察其对体外细胞增殖和胶原溶解的影响。结果在CNA和非CNA样品中，western blot检测到VIP的光带，而在CNA和非CNA样品中均检测到丰富的丙氨酸。大多数CNA样本(5/6)CGRP表达增加，平均条带密度约为非CNA组的2倍(p <. 05)。CGRP免疫组化结果显示，CGRP在CNA滑膜内膜呈强染色。在组织培养中，在培养基中添加CGRP (10 nM)可促进FLS增殖。CGRP联合TNF-α可增强体外fls介导的胶原溶解。结论CGRP在CNA滑膜中表达增加，并可调节FLS增殖和胶原溶解活性，提示CGRP可能参与CNA骨和软骨破坏。

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来源期刊

Experimental and molecular pathology 医学-病理学

CiteScore

8.90

自引率

0.00%

发文量

审稿时长

11.5 weeks

期刊介绍： Under new editorial leadership, Experimental and Molecular Pathology presents original articles on disease processes in relation to structural and biochemical alterations in mammalian tissues and fluids and on the application of newer techniques of molecular biology to problems of pathology in humans and other animals. The journal also publishes selected interpretive synthesis reviews by bench level investigators working at the "cutting edge" of contemporary research in pathology. In addition, special thematic issues present original research reports that unravel some of Nature''s most jealously guarded secrets on the pathologic basis of disease. Research Areas include: Stem cells; Neoangiogenesis; Molecular diagnostics; Polymerase chain reaction; In situ hybridization; DNA sequencing; Cell receptors; Carcinogenesis; Pathobiology of neoplasia; Complex infectious diseases; Transplantation; Cytokines; Flow cytomeric analysis; Inflammation; Cellular injury; Immunology and hypersensitivity; Athersclerosis.