{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:31:42Z","timestamp":1786977102981,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,4,5]],"date-time":"2004-04-05T00:00:00Z","timestamp":1081123200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"DFG","award":["Str 511\/10-1"],"award-info":[{"award-number":["Str 511\/10-1"]}]},{"name":"DFG","award":["Str 511\/11-1"],"award-info":[{"award-number":["Str 511\/11-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The presence of selective sympathetic nerve repellents, i.e., semaphorins, may be responsible for the observed reduction of sympathetic innervation in the synovial tissue of patients with rheumatoid arthritis (RA). This study was undertaken to investigate the presence of different semaphorins in synovial tissue of patients with RA, patients with osteoarthritis (OA), and control subjects without inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In situ hybridizations with digoxigenin\u2010labeled RNA probes directed against different semaphorins were performed. The presence of semaphorin 3C (S3C) in the synovial tissue of 10 RA, 10 OA, and 5 control subjects was investigated using a polyclonal antiserum directed against S3C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All in situ hybridizations revealed the presence of S3C messenger RNA, but no other investigated semaphorin (i.e., against primary afferent sensory nerve fibers), in the synovial tissue of RA and OA patients. Immunohistologic double staining demonstrated that macrophages and fibroblasts were positive for S3C protein. Quantitative analysis of S3C protein staining showed an increased density of S3C\u2010positive cells in the synovial tissue of RA patients (mean \u00b1 SEM 339 \u00b1 65 cells\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ) in comparison with OA patients (168 \u00b1 27\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.031 versus RA) and controls (126 \u00b1 26\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.027 versus RA). Studies of the relationship between sympathetic nerve fiber density and S3C\u2010positive cell density in the tissue of all patients showed that RA patients generally had lower densities of sympathetic nerve fibers and higher densities of S3C\u2010positive cells than OA patients and control subjects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that S3C from macrophages and fibroblasts, which is selectively directed against sympathetic nerve fibers, could be one element responsible for reduced sympathetic innervation in RA tissue. The inability of sympathetic nerve fibers to reinnervate synovial tissue could contribute to the chronic nature of RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.20110","type":"journal-article","created":{"date-parts":[[2004,4,5]],"date-time":"2004-04-05T12:02:06Z","timestamp":1081166526000},"page":"1156-1163","source":"Crossref","is-referenced-by-count":95,"title":["Increased prevalence of semaphorin 3C, a repellent of sympathetic nerve fibers, in the synovial tissue of patients with rheumatoid arthritis"],"prefix":"10.1002","volume":"50","author":[{"given":"Luitpold E.","family":"Miller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Weidler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Falk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Angele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Schaumburger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Sch\u00f6lmerich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer H.","family":"Straub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,4,5]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0889-857X(21)00853-X","article-title":"Contribution of the nervous system to the pathophysiology of rheumatoid arthritis and other polyarthritides","volume":"13","author":"Levine JD","year":"1987","journal-title":"Rheum Dis Clin North Am"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370701"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200103)44:3<493::AID-ANR95>3.0.CO;2-U"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb07649.x"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.145.5.1430"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0085com"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-1082com"},{"key":"e_1_2_5_9_2","first-page":"427","article-title":"Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritis","volume":"29","author":"Miller LE","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)64012-1"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/2154"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050934"},{"key":"e_1_2_5_13_2","first-page":"433","article-title":"Nerve growth factor and autoimmune rheumatic diseases","volume":"15","author":"Aloe L","year":"1997","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022475432077"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004180000222"},{"key":"e_1_2_5_16_2","unstructured":"Non\u2010radioactive in situ hybridization application manual. 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