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Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis

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Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis

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dc.contributor.author Nacher-Juan, Josep es_ES
dc.contributor.author Terencio Silvestre, Mª Carmen es_ES
dc.contributor.author Alcaraz Tormo, Mª José es_ES
dc.contributor.author Ferrandiz Manglano, Mª Luisa es_ES
dc.date.accessioned 2020-06-06T03:32:46Z
dc.date.available 2020-06-06T03:32:46Z
dc.date.issued 2019-08-07 es_ES
dc.identifier.uri http://hdl.handle.net/10251/145549
dc.description.abstract [EN] In chronic inflammatory joint diseases, such as rheumatoid arthritis, there is an important bone loss. Parathyroid hormone-related protein (PTHrP) and related peptides have shown osteoinductive properties in bone regeneration models, but there are no data on inflammatory joint destruction. We have investigated whether the PTHrP (107-111) C-terminal peptide (osteostatin) could control the development of collagen-induced arthritis in mice. Administration of osteostatin (80 or 120 mu g/kg s.c.) after the onset of disease decreased the severity of arthritis as well as cartilage and bone degradation. This peptide reduced serum IgG2a levels as well as T cell activation, with the downregulation of ROR gamma t+CD4+ T cells and upregulation of FoxP3+CD8+ T cells in lymph nodes. The levels of key cytokines, such as interleukin(IL)-1 beta, IL-2, IL-6, IL-17, and tumor necrosis factor-alpha in mice paws were decreased by osteostatin treatment, whereas IL-10 was enhanced. Bone protection was related to reductions in receptor activator of nuclear factor-kappa B ligand, Dickkopf-related protein 1, and joint osteoclast area. Osteostatin improves arthritis and controls bone loss by inhibiting immune activation, pro-inflammatory cytokines, and osteoclastogenesis. Our results support the interest of osteostatin for the treatment of inflammatory joint conditions. es_ES
dc.description.sponsorship This work has been funded by grant SAF2017-85806-R (Ministerio de Ciencia, Innovación y Universidades, Spain, FEDER). J. Nácher-Juan thanks Universitat de València, Spain, for a PhD fellowship (INV18-01-13-01). es_ES
dc.language Inglés es_ES
dc.publisher MDPI AG es_ES
dc.relation.ispartof International Journal of Molecular Sciences es_ES
dc.rights Reconocimiento (by) es_ES
dc.subject Osteostatin es_ES
dc.subject Arthritis es_ES
dc.subject Inflammation es_ES
dc.subject Immune response es_ES
dc.subject Cartilage destruction es_ES
dc.subject Bone erosion es_ES
dc.title Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.3390/ijms20163845 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/UV//INV18-01-13-01/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-85806-R/ES/MECANISMOS REGULADORES DE LA INFLAMACION Y SU RESOLUCION EN ENFERMEDADES CRONICAS ARTICULARES Y DE LA PIEL/ es_ES
dc.rights.accessRights Abierto es_ES
dc.description.bibliographicCitation Nacher-Juan, J.; Terencio Silvestre, MC.; Alcaraz Tormo, MJ.; Ferrandiz Manglano, ML. (2019). Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis. International Journal of Molecular Sciences. 20(16):1-18. https://doi.org/10.3390/ijms20163845 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.3390/ijms20163845 es_ES
dc.description.upvformatpinicio 1 es_ES
dc.description.upvformatpfin 18 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 20 es_ES
dc.description.issue 16 es_ES
dc.identifier.eissn 1422-0067 es_ES
dc.identifier.pmid 31394717 es_ES
dc.identifier.pmcid PMC6721041 es_ES
dc.relation.pasarela S\403069 es_ES
dc.contributor.funder Universitat de València es_ES
dc.contributor.funder Agencia Estatal de Investigación es_ES
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