{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T02:42:30Z","timestamp":1776652950117,"version":"3.51.2"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2005,6,23]],"date-time":"2005-06-23T00:00:00Z","timestamp":1119484800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,6,23]],"date-time":"2005-06-23T00:00:00Z","timestamp":1119484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by the presence of inflammatory synovitis accompanied by destruction of joint cartilage and bone. Treatment with vasoactive intestinal peptide (VIP) prevents experimental arthritis in animal models by downregulation of both autoimmune and inflammatory components of the disease. The aim of this study was to characterize the protective effect of VIP on bone erosion in collagen-induced arthritis (CIA) in mice. We have studied the expression of different mediators implicated in bone homeostasis, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), receptor activator of nuclear factor-\u03baB (RANK), receptor activator of nuclear factor-\u03baB ligand (RANKL), osteoprotegerin (OPG), IL-1, IL-4, IL-6, IL-10, IL-11 and IL-17. Circulating cytokine levels were assessed by ELISA and the local expression of mediators were determined by RT-PCR in mRNA extracts from joints. VIP treatment resulted in decreased levels of circulating IL-6, IL-1\u03b2 and TNF\u03b1, and increased levels of IL-4 and IL-10. CIA-mice treated with VIP presented a decrease in mRNA expression of IL-17, IL-11 in the joints. The ratio of RANKL to OPG decreased drastically in the joint after VIP treatment, which correlated with an increase in levels of circulating OPG in CIA mice treated with VIP. In addition, VIP treatment decreased the expression of mRNA for RANK, iNOS and COX-2. To investigate the molecular mechanisms involved, we tested the activity of NF\u03baB and AP-1, two transcriptional factors closely related to joint erosion, by EMSA in synovial cells from CIA mice. VIP treatment <jats:italic>in vivo<\/jats:italic> was able to affect the transcriptional activity of both factors. Our data indicate that VIP is a viable candidate for the development of treatments for RA.<\/jats:p>","DOI":"10.1186\/ar1779","type":"journal-article","created":{"date-parts":[[2005,6,23]],"date-time":"2005-06-23T18:13:40Z","timestamp":1119550420000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Protective effect of vasoactive intestinal peptide on bone destruction in the collagen-induced arthritis model of rheumatoid arthritis"],"prefix":"10.1186","volume":"7","author":[{"given":"Yasmina","family":"Juarranz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catalina","family":"Abad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Arranz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Gutierrez-Ca\u00f1as","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florencia","family":"Rosignoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa P","family":"Gomariz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Leceta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2005,6,23]]},"reference":[{"key":"1658_CR1","doi-asserted-by":"publisher","first-page":"ii84","DOI":"10.1136\/ard.61.suppl_2.ii84","volume":"61","author":"EM Gravallese","year":"2002","unstructured":"Gravallese EM: Bone destruction in arthritis. Ann Rheum Dis. 2002, 61: ii84-ii86.","journal-title":"Ann Rheum Dis"},{"key":"1658_CR2","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/1529-0131(200002)43:2<259::AID-ANR4>3.0.CO;2-W","volume":"43","author":"H Takayanagi","year":"2000","unstructured":"Takayanagi H, Iizuka H, Juji T, Nakagawa T, Yamamoto A, Myazaki T, Koshihara Y, Oda H, Nakamura K, Tanaka S: Involvement of receptor activator of nuclear factor kB ligand\/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum. 2000, 43: 259-269. 10.1002\/1529-0131(200002)43:2<259::AID-ANR4>3.0.CO;2-W.","journal-title":"Arthritis Rheum"},{"key":"1658_CR3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/1529-0131(200102)44:2<253::AID-ANR41>3.0.CO;2-S","volume":"44","author":"LC Hofbauer","year":"2001","unstructured":"Hofbauer LC, Heulfelder AE: The role of osteoprotegerin and receptor activator of nuclear factor kappaB ligand in the pathogenesis and treatment of rheumatoid arthritis. Arthritis Rheum. 2001, 44: 253-259. 10.1002\/1529-0131(200102)44:2<253::AID-ANR41>3.0.CO;2-S.","journal-title":"Arthritis Rheum"},{"key":"1658_CR4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1097\/00002281-200305000-00016","volume":"15","author":"T Nakashima","year":"2003","unstructured":"Nakashima T, Wada T, Penninger JM: RANKL and RANK as novel therapeutic targets for arthritis. Curr Opin Rheumatol. 2003, 15: 280-287. 10.1097\/00002281-200305000-00016.","journal-title":"Curr Opin Rheumatol"},{"key":"1658_CR5","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1136\/ard.2003.008458","volume":"63","author":"D O'Gradaigh","year":"2004","unstructured":"O'Gradaigh D, Ireland D, Bord S, Compston JE: Joint erosion in rheumatoid arthritis: interactions between tumor necrosis factor \u03b1, interleukin 1, and receptor activator of nuclear factor kB ligand (RANKL) regulate osteoclasts. Ann Rheum Dis. 2004, 63: 354-359. 10.1136\/ard.2003.008458.","journal-title":"Ann Rheum Dis"},{"key":"1658_CR6","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1016\/S0024-3205(97)00480-3","volume":"61","author":"LK Myers","year":"1878","unstructured":"Myers LK, Rosloniec EF, Cremer MA, Kang AH: Collagen-induced arthritis, an animal model of autoimmunity. Life Sci. 1878, 61: 1861-1872. 10.1016\/S0024-3205(97)00480-3.","journal-title":"Life Sci"},{"key":"1658_CR7","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1002\/art.10607","volume":"46","author":"E Lubberts","year":"2002","unstructured":"Lubberts E, Oppers-Walgreen B, Pettit AR, van den Bersselaar L, Joosten LAB, Goldring SR, Gravallese EM, van den Berg WB: Increase in expression of receptor activator of nuclear factor \u03baB at sites of bone erosion correlates with progression of inflammation in evolving collagen-induced arthritis. Arthritis Rheum. 2002, 46: 3055-3064. 10.1002\/art.10607.","journal-title":"Arthritis Rheum"},{"key":"1658_CR8","first-page":"189","volume":"19","author":"HC Blair","year":"2004","unstructured":"Blair HC, Athanasou NA: Recent advances in osteoclast biology and pathological bone resorption. Histol Histopathol. 2004, 19: 189-199.","journal-title":"Histol Histopathol"},{"key":"1658_CR9","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/S8756-3282(02)00784-6","volume":"31","author":"J Ahlen","year":"2002","unstructured":"Ahlen J, Andersson S, Mukohyama H, Roth C, B\u00e4ckman A, Conaway HH, Lerner UH: Characterization of the bone-resorptive effect of interleukin-11 in cultured mouse calvarial bones. Bone. 2002, 31: 242-251. 10.1016\/S8756-3282(02)00784-6.","journal-title":"Bone"},{"key":"1658_CR10","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.4049\/jimmunol.170.5.2655","volume":"170","author":"E Lubberts","year":"2003","unstructured":"Lubberts E, van den Bersselaar L, Oppers-Walgreen B, Schwarzenberger P, Coenen-de Roo CJJ, Kolls JK, Joosten LAB, van den Berg WB: IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kB ligand\/osteoprotegerin balance. J Immunol. 2003, 170: 2655-2662.","journal-title":"J Immunol"},{"key":"1658_CR11","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1006\/bbrc.1998.9788","volume":"253","author":"N Nakagawa","year":"1998","unstructured":"Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K, Morinaga T, Higashio K: RANK is the essential signaling receptor for osteoclast differentiation factor in ostoclastogenesis. Biochem Biophys Res Commun. 1998, 253: 395-400. 10.1006\/bbrc.1998.9788.","journal-title":"Biochem Biophys Res Commun"},{"key":"1658_CR12","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature01658","volume":"423","author":"WJ Boyle","year":"2003","unstructured":"Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and activation. Nature. 2003, 423: 337-342. 10.1038\/nature01658.","journal-title":"Nature"},{"key":"1658_CR13","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","volume":"289","author":"SL Teitelbaum","year":"2000","unstructured":"Teitelbaum SL: Bone resorption by osteoclast. Science. 2000, 289: 1504-1508. 10.1126\/science.289.5484.1504.","journal-title":"Science"},{"key":"1658_CR14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S1297-319X(03)00131-3","volume":"71","author":"N Saidenberg-Kermanac'h","year":"2004","unstructured":"Saidenberg-Kermanac'h N, Cohen-Solal M, Bessis N, De Vernejoul MC, Boissier MC: Role of osteoprotegerin in rheumatoid inflammation. Joint Bone Spine. 2004, 71: 9-13. 10.1016\/S1297-319X(03)00131-3.","journal-title":"Joint Bone Spine"},{"key":"1658_CR15","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/0889-1591(90)90017-K","volume":"4","author":"RP Gomariz","year":"1990","unstructured":"Gomariz RP, Lorenzo MJ, Cacicedo L, Vicente A, Zapata AG: Demonstration of immunoreactive vasoactive intestinal peptide (IR-VIP) and somatostatin (IR-SOM) in rat thymus. Brain Behav Immun. 1990, 4: 151-161. 10.1016\/0889-1591(90)90017-K.","journal-title":"Brain Behav Immun"},{"key":"1658_CR16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.2174\/1381612013398374","volume":"7","author":"RP Gomariz","year":"2001","unstructured":"Gomariz RP, Martinez C, Abad C, Leceta J, Delgado M: Immunobiology of VIP: a review and therapeutical perspectives. Curr Pharm Des. 2001, 7: 89-111. 10.2174\/1381612013398374.","journal-title":"Curr Pharm Des"},{"key":"1658_CR17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s00109-001-0291-5","volume":"80","author":"M Delgado","year":"2002","unstructured":"Delgado M, Abad C, Martinez C, Juarranz MG, Arranz A, Gomartiz RP, Leceta J: Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune disease. J Mol Med. 2002, 80: 16-24. 10.1007\/s00109-001-0291-5.","journal-title":"J Mol Med"},{"key":"1658_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14748\/bmr.v12.120","volume":"12","author":"RP Gomariz","year":"2001","unstructured":"Gomariz RP, Abad C, Martinez C, Juarranz MG, da Costa S, Arranz A, Delgado M, Leceta J: Vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and immune system: from basic research to potential clinical application. Biomedical Rev. 2001, 12: 1-9.","journal-title":"Biomedical Rev"},{"key":"1658_CR19","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1124\/pr.56.2.7","volume":"56","author":"M Delgado","year":"2004","unstructured":"Delgado M, Pozo D, Ganea D: The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev. 2004, 56: 249-290. 10.1124\/pr.56.2.7.","journal-title":"Pharmacol Rev"},{"key":"1658_CR20","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.4049\/jimmunol.162.2.1200","volume":"162","author":"M Delgado","year":"1999","unstructured":"Delgado M, Martinez C, Pozo D, Calvo JR, Leceta J, Ganea D, Gomariz RP: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activation polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition of TNF-alpha and IL-6. J Immunol. 1999, 162: 1200-1205.","journal-title":"J Immunol"},{"key":"1658_CR21","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1053\/gast.2003.50141","volume":"124","author":"C Abad","year":"2003","unstructured":"Abad C, Martinez C, Juarranz MG, Arranz A, Leceta J, Delgado M, Gomariz RP: Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease. Gastroenterology. 2003, 124: 961-971.","journal-title":"Gastroenterology"},{"key":"1658_CR22","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/87887","volume":"7","author":"M Delgado","year":"2001","unstructured":"Delgado M, Abad C, Martinez C, Leceta J, Gomariz RP: Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med. 2001, 7: 563-568. 10.1038\/87887.","journal-title":"Nat Med"},{"key":"1658_CR23","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1093\/rheumatology\/keh061","volume":"43","author":"MG Juarranz","year":"2004","unstructured":"Juarranz MG, Santiago B, Torroba M, Gutierrez-Ca\u00f1as I, Palao G, Galindo M, Abad C, Martinez C, Leceta J, Pablos JL, Gomariz RP: Vasoactive intestinal peptide modulates proinflammatory mediator synthesis in osteoartritic and rheumatoid synovial cells. Rheumatology (Oxford). 2004, 43: 416-422. 10.1093\/rheumatology\/keh061.","journal-title":"Rheumatology (Oxford)"},{"key":"1658_CR24","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0167-0115(99)00069-5","volume":"85","author":"P Lundberg","year":"1999","unstructured":"Lundberg P, Bostr\u00f6m I, Mukohyama H, Bjurholm A, Smans K, Lerner UH: Neuro-hormonal control of bone metabolism: vasoactive intestinal peptide stimulates alkaline phosphatase activity and mRNA expression in mouse calvarial osteoblasts as well as calcium accumulation mineralized bone nodules. Regul Pept. 1999, 85: 47-58. 10.1016\/S0167-0115(99)00069-5.","journal-title":"Regul Pept"},{"key":"1658_CR25","first-page":"265","volume":"50","author":"AJ Harmar","year":"1998","unstructured":"Harmar AJ, Arimura A, Gozes I, Journot L, Laburthe M, Pisegna JR, Rawlings SR, Robberecht P, Said SI, Sreedharan SP, et al: International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev. 1998, 50: 265-270.","journal-title":"Pharmacol Rev"},{"key":"1658_CR26","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1006\/bbrc.2000.3151","volume":"274","author":"M Ransj\u00f6","year":"2000","unstructured":"Ransj\u00f6 M, Lie A, Mukohyama H, Lundberg P, Lerner UH: Microisolated mouse osteoclasts express VIP-1 and PACAP receptors. Biochem Biophys Res Commun. 2000, 274: 400-404. 10.1006\/bbrc.2000.3151.","journal-title":"Biochem Biophys Res Commun"},{"key":"1658_CR27","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1210\/en.142.1.339","volume":"142","author":"P Lundberg","year":"2001","unstructured":"Lundberg P, Lundgren I, Mukohyama H, Lehenkari PP, Horton MA, Lerner UH: Vasoactive intestinal peptide (VIP)\/pituitary adenylate cyclase-activating peptide receptor subtypes in mouse calvarian osteoblasts: presence of VIP-2 receptors and differentiation-induced expression of VIP-1 receptors. Endocrinology. 2001, 142: 339-347. 10.1210\/en.142.1.339.","journal-title":"Endocrinology"},{"key":"1658_CR28","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1006\/bbrc.2000.2599","volume":"271","author":"H Mukohyama","year":"2000","unstructured":"Mukohyama H, Ransj\u00f6 M, Taniguchi H, Ohyama T, Lerner UH: The inhibitory effects of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide on osteoclast formation are associated with upregulation of osteoprotegerin and downregulation of RANKL and RANK. Biochem Biophys Res Commun. 2000, 271: 158-163. 10.1006\/bbrc.2000.2599.","journal-title":"Biochem Biophys Res Commun"},{"key":"1658_CR29","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1677\/jme.0.0250169","volume":"25","author":"SA Bustin","year":"2000","unstructured":"Bustin SA: Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000, 25: 169-193. 10.1677\/jme.0.0250169.","journal-title":"J Mol Endocrinol"},{"key":"1658_CR30","doi-asserted-by":"publisher","first-page":"6419","DOI":"10.1093\/nar\/17.15.6419","volume":"17","author":"E Schreiber","year":"1989","unstructured":"Schreiber E, Metthias P, Muller W, Shaffner W: Rapid detection of octamer binding proteins with \"mini-extracts\" prepared from a small number of cells. Nucleic Acids Res. 1989, 17: 6419-","journal-title":"Nucleic Acids Res"},{"key":"1658_CR31","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/ar14","volume":"1","author":"LAB Joosten","year":"1999","unstructured":"Joosten LAB, Lubberts E, Helsen MMA, Saxne T, Coenen-de Roo CJJ, Heinegard D, van den Berg W: Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis. Arthritis Res. 1999, 1: 81-91. 10.1186\/ar14.","journal-title":"Arthritis Res"},{"key":"1658_CR32","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/nm1054","volume":"10","author":"E Jimi","year":"2004","unstructured":"Jimi E, Aoki K, Saito H, D\u00c0cquisto F, May MJ, Nakamura I, Sudo T, Kojima T, Okamoto F, Fukushima H, et al: Selective inhibition of NF-kB blocks osteoclastogenesis and prevents inflammatory bone destrction in vivo. Nature Medicine. 2004, 10: 617-624. 10.1038\/nm1054.","journal-title":"Nature Medicine"},{"key":"1658_CR33","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1172\/JCI200419657","volume":"114","author":"F Ikeda","year":"2004","unstructured":"Ikeda F, Nishimura R, Matsubara T, Tanaka S, Inoue JI, Reddy S, Hata K, Yamashita K, Hiraga T, Watanabe T, et al: Critical roles of c-Jun signalling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. J Clin Invest. 2004, 114: 475-484. 10.1172\/JCI200419657.","journal-title":"J Clin Invest"},{"key":"1658_CR34","doi-asserted-by":"publisher","first-page":"28355","DOI":"10.1074\/jbc.273.43.28355","volume":"273","author":"BR Wong","year":"1998","unstructured":"Wong BR, Josien R, Lee Sy, Vologodskaia M, Steinman RM, Choin Y: The TRAF family of signal transducers mediates NF-kappa B activation by the TRANCE receptor. J Biol Chem. 1998, 273: 28355-28359. 10.1074\/jbc.273.43.28355.","journal-title":"J Biol Chem"},{"key":"1658_CR35","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1074\/jbc.M006923200","volume":"276","author":"M Delgado","year":"2001","unstructured":"Delgado M, Ganea D: Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit nuclear factor-kB-dependent gene activation at multiple levels in the human monocytic cell line THP-1. J Biol Chem. 2001, 276: 369-380. 10.1074\/jbc.M006923200.","journal-title":"J Biol Chem"},{"key":"1658_CR36","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/j.1749-6632.2000.tb06954.x","volume":"921","author":"J Leceta","year":"2000","unstructured":"Leceta J, Gomariz RP, Martinez C, Abad C, Ganea D, Delgado M: Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP. Ann NY Acad Sci. 2000, 921: 92-102.","journal-title":"Ann NY Acad Sci"},{"key":"1658_CR37","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0165-5728(00)00359-3","volume":"110","author":"M Delgado","year":"2000","unstructured":"Delgado M, Ganea D: Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide inhibit the MEKK1\/MEK4\/JNK signaling pathway in LPS-stimulated macrophages. J Neuroimmunol. 2000, 110: 97-105. 10.1016\/S0165-5728(00)00359-3.","journal-title":"J Neuroimmunol"},{"key":"1658_CR38","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/S8756-3282(00)00394-X","volume":"27","author":"P Lundberg","year":"2000","unstructured":"Lundberg P, Lie A, Bjurholm A, Lehenkari PP, Horton MA, Lerner UH, Ransj\u00f6 M: Vasoactive intestinal peptide regulates osteoclast activity via specific binding sites on both osteoclasts and osteoblasts. Bone. 2000, 27: 803-810. 10.1016\/S8756-3282(00)00394-X.","journal-title":"Bone"},{"key":"1658_CR39","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/ar136","volume":"3","author":"WB Van den Berg","year":"2001","unstructured":"Van den Berg WB: Anti-cytokine therapy in chronic destructive arthritis. Arthritis Res. 2001, 3: 18-26. 10.1186\/ar136.","journal-title":"Arthritis Res"},{"key":"1658_CR40","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.4049\/jimmunol.163.9.5049","volume":"163","author":"LAB Joosten","year":"1999","unstructured":"Joosten LAB, Helsen MMA, Saxne T, van de Loo FAJ, Heinegard D, van den Berg WB: IL-1\u03b1\u03b2 blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-a blockade only ameliorates joint inflammation. J Immunol. 1999, 163: 5049-5055.","journal-title":"J Immunol"},{"key":"1658_CR41","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1084\/jem.187.1.129","volume":"187","author":"R Bonecchi","year":"1998","unstructured":"Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F: Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med. 1998, 187: 129-134. 10.1084\/jem.187.1.129.","journal-title":"J Exp Med"},{"key":"1658_CR42","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1084\/jem.20030015","volume":"197","author":"C Miyaura","year":"2003","unstructured":"Miyaura C, Inada M, Matsumoto C, Ohshiba T, Uozumi N, Shimuzu T, Ito A: An essential role of cytosolic phospholipase A2\u03b1 in prostaglandin E2-mediated bone resorption associated with inflammation. J Exp Med. 2003, 197: 1303-1310. 10.1084\/jem.20030015.","journal-title":"J Exp Med"},{"key":"1658_CR43","doi-asserted-by":"publisher","first-page":"7993","DOI":"10.1073\/pnas.130511497","volume":"97","author":"RJ Van't Hof","year":"2000","unstructured":"Van't Hof RJ, Armour KJ, Smith LM, Armour KE, Wei XQ, Liew FY, Ralston SH: Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption. Proc Natl Acad Sci USA. 2000, 97: 7993-7998. 10.1073\/pnas.130511497.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1658_CR44","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1046\/j.1365-2249.2002.01913.x","volume":"129","author":"R Gerli","year":"2002","unstructured":"Gerli R, Bistoni O, Russano A, Fiorucci S, Borgato L, Cesarotti MEF, Lunardi C: In vivo activated T cells in rheumatoid synovitis. Analysis of Th1-and Th2-type cytokine production at clonal level in different stages of disease. Clin Exp Immunol. 2002, 129: 549-555. 10.1046\/j.1365-2249.2002.01913.x.","journal-title":"Clin Exp Immunol"},{"key":"1658_CR45","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1006\/bbrc.1999.1623","volume":"265","author":"NJ Horwood","year":"1999","unstructured":"Horwood NJ, Kartsogiannis V, Quinn JMW, Romas E, Martin TJ, Gillespie MT: Activated T lymphocytes support osteoclast formation in vitro. Biochim Biophys Res Commun. 1999, 265: 144-150. 10.1006\/bbrc.1999.1623.","journal-title":"Biochim Biophys Res Commun"},{"key":"1658_CR46","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.4049\/jimmunol.162.3.1246","volume":"162","author":"T Aarvak","year":"1999","unstructured":"Aarvak T, Chabaud M, Miossec P, Natvig JB: IL-17 is produced by some proinflammatory Th1\/Th0 cells but not by Th2 cells. J Immunol. 1999, 162: 1246-1251.","journal-title":"J Immunol"},{"key":"1658_CR47","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1182\/blood.V100.7.2530","volume":"100","author":"JK Walton","year":"2002","unstructured":"Walton JK, Duncan JM, Deschamps P, Shaughnessy SG: Heparin acts synergistically with interleukin-11 to induce STAT3 activation and in vitro osteoclast formation. Blood. 2002, 100: 2530-2536. 10.1182\/blood.V100.7.2530.","journal-title":"Blood"},{"key":"1658_CR48","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1053\/berh.2001.0187","volume":"15","author":"H Schulze-Koops","year":"2001","unstructured":"Schulze-Koops H, Kalden JR: The balance of Th1\/Th2 cytokines in rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2001, 15: 677-691. 10.1053\/berh.2001.0187.","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"1658_CR49","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/S8756-3282(01)00682-2","volume":"30","author":"E Romas","year":"2002","unstructured":"Romas E, Gillespie MT, Martin TJ: Involvement of receptor activator of NFkB ligand and tumor necrosis factor-\u03b1 in bone destruction in rheumatoid arthritis. Bone. 2002, 30: 340-346. 10.1016\/S8756-3282(01)00682-2.","journal-title":"Bone"},{"key":"1658_CR50","doi-asserted-by":"publisher","first-page":"ii32","DOI":"10.1136\/ard.61.suppl_2.ii32","volume":"61 Suppl","author":"DH Jones","year":"2002","unstructured":"Jones DH, Kong Y-Y, Penninger JM: Role of RANKL and RANK in bone loss and arthritis. Ann Rheum Dis. 2002, 61 Suppl: ii32-ii39. 10.1136\/ard.61.2.182-a.","journal-title":"Ann Rheum Dis"},{"key":"1658_CR51","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S1044-5323(02)00124-0","volume":"15","author":"Z Szekanecz","year":"2003","unstructured":"Szekanecz Z, Kim J, Koch AE: Chemokines and chemokine receptors in rheumatoid arthritis. Semin Immunol. 2003, 15: 15-21. 10.1016\/S1044-5323(02)00124-0.","journal-title":"Semin Immunol"},{"key":"1658_CR52","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/46303","volume":"402","author":"Y-Y Kong","year":"1999","unstructured":"Kong Y-Y, Feige U, Sarosi I, Bolon B, Tarufi A, Morony S, Capparelli C, Li J, Elliot R, McCabe S, et al: Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999, 402: 304-309. 10.1038\/46303.","journal-title":"Nature"},{"key":"1658_CR53","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/nrd1109","volume":"2","author":"JS Smolen","year":"2003","unstructured":"Smolen JS, Steiner G: Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov. 2003, 2: 473-488. 10.1038\/nrd1109.","journal-title":"Nat Rev Drug Discov"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar1779.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar1779\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar1779.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:38:08Z","timestamp":1728383888000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar1779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,23]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2005,9]]}},"alternative-id":["1658"],"URL":"https:\/\/doi.org\/10.1186\/ar1779","relation":{},"ISSN":["1478-6354"],"issn-type":[{"value":"1478-6354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,23]]},"assertion":[{"value":"6 April 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2005","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2005","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2005","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R1034"}}