Yi Guo , Lew Schon , Sharada Paudel , Tyler Feltham , Lumanti Manandhar , Zijun Zhang
{"title":"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","authors":"Yi Guo , Lew Schon , Sharada Paudel , Tyler Feltham , Lumanti Manandhar , Zijun Zhang","doi":"10.1016/j.yexmp.2022.104835","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Joint destruction in Charcot neuroarthropathy (CNA) is accompanied with abundant hyperplastic synovium<span>. This study aimed to characterize the expression patterns of a group of neuropeptides in the CNA synovium.</span></p></div><div><h3>Methods</h3><p>Synovial specimens were collected during surgery from the CNA (<em>n</em> = 6) and non-CNA joints (<em>n</em><span><span><span> = 14). Tissue samples were processed for protein extraction and western blot<span> for vasoactive intestinal peptide (VIP), </span></span>galanin<span>, and calcitonin gene-related peptide (CGRP). Immunohistochemistry<span> was performed to localize CGRP in the CNA synovium. Additionally, CGRP was applied to fibroblast-like synoviocytes<span> (FLS) isolated from CNA synovium for its effects on cell proliferation and </span></span></span></span>collagenolysis </span><em>in vitro</em>.</p></div><div><h3>Results</h3><p>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 (<em>p < .05</em>). 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 <em>in vitro</em>.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104835"},"PeriodicalIF":2.8000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Increased synovial expression of calcitonin gene-related peptide and its potential roles in Charcot Neuroarthropathy\",\"authors\":\"Yi Guo , Lew Schon , Sharada Paudel , Tyler Feltham , Lumanti Manandhar , Zijun Zhang\",\"doi\":\"10.1016/j.yexmp.2022.104835\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Joint destruction in Charcot neuroarthropathy (CNA) is accompanied with abundant hyperplastic synovium<span>. This study aimed to characterize the expression patterns of a group of neuropeptides in the CNA synovium.</span></p></div><div><h3>Methods</h3><p>Synovial specimens were collected during surgery from the CNA (<em>n</em> = 6) and non-CNA joints (<em>n</em><span><span><span> = 14). Tissue samples were processed for protein extraction and western blot<span> for vasoactive intestinal peptide (VIP), </span></span>galanin<span>, and calcitonin gene-related peptide (CGRP). Immunohistochemistry<span> was performed to localize CGRP in the CNA synovium. Additionally, CGRP was applied to fibroblast-like synoviocytes<span> (FLS) isolated from CNA synovium for its effects on cell proliferation and </span></span></span></span>collagenolysis </span><em>in vitro</em>.</p></div><div><h3>Results</h3><p>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 (<em>p < .05</em>). 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 <em>in vitro</em>.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":12176,\"journal\":{\"name\":\"Experimental and molecular pathology\",\"volume\":\"128 \",\"pages\":\"Article 104835\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2022-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental and molecular pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014480022000983\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and molecular pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014480022000983","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
Increased synovial expression of calcitonin gene-related peptide and its potential roles in Charcot Neuroarthropathy
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.
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.