{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:27:55Z","timestamp":1791419275945,"version":"4.3.3"},"reference-count":48,"publisher":"BMJ","issue":"2","funder":[{"DOI":"10.13039\/100020555","name":"Ospedale Pediatrico Bambino Gesu","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020555","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2017,6,16]]},"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To identify the role of mature nerve growth factor (mNGF), its immature form proNGF and their receptors in arthritis inflammation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Real-time PCR, western blot and ELISA were performed to evaluate NGF, proNGF, their receptor and cytokine expression in synovial tissue and cells of patients with juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA), and controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>proNGF and not mNGF is the prevalent form measured in synovial fluids of patients with JIA and RA with synovial fibroblasts as a major source of proNGF in the inflamed synoviae. p75NTR, the specific receptor for proNGF, is the NGF receptor most expressed in mononuclear cells of patients with JIA, while TrkA is the prevalent receptor in healthy donors. In ex vivo experiments the effects of proNGF differ from those of mNGF, suggesting that the balance of p75NTR and TrkA expression represents a critical factor in regulating mNGF\/proNGF functions, determining which intracellular pathways and biological activities are triggered. Contrary to NGF, proNGF administration increased inflammatory cytokines but not interleukin (IL)-10 expression, inducing a stronger activation of p38 and JNK pathways. proNGF effects depend on its binding to p75NTR, as inhibition of p75NTR with neutralising antibodies or LM11A-31 abolished proNGF-induced production of IL-6 in patients\u2019 mononuclear cells, while inhibition of TrkA did not. There is a correlation in patients with arthritis between high p75NTR levels and severity of clinical symptoms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data suggest that an active proNGF-p75NTR axis promotes proinflammatory mechanisms contributing to chronic tissue inflammation, and that the use of p75NTR inhibitors may represent a new therapeutic approach in chronic arthritis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2017-000441","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T20:10:31Z","timestamp":1505247031000},"page":"e000441","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["ProNGF-p75NTR axis plays a proinflammatory role in inflamed joints: a novel pathogenic mechanism in chronic arthritis"],"prefix":"10.1136","volume":"3","clinical-trial-number":[{"clinical-trial-number":"nct03069014","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Gaetana","family":"Minnone","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Soligo","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche (CNR), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Caiello","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusi","family":"Prencipe","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Manni","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche (CNR), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Pires","family":"Marafon","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Magni-Manzoni","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Manzo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Translational Immunology Research Laboratories (LaRIT), IRCCS Policlinico S Matteo Foundation\/University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"De Benedetti","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bracci-Laudiero","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immuno-Rheumatology Research Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, Rome, Italy"},{"name":"Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche (CNR), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2017,9,12]]},"reference":[{"key":"2025090313535025000_3.2.e000441.1","unstructured":"Bracci-Laudiero L . 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