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dc.contributor.authorPortal-Núñez, Sergio
dc.contributor.authorArdura, J. A.
dc.contributor.authorLozano, D.
dc.contributor.authorMartínez de Toda, I.
dc.contributor.authorDe La Fuente, M.
dc.contributor.authorHerrero-Beaumont Cuenca, Gabriel 
dc.contributor.authorLargo, R.
dc.contributor.authorEsbrit, P.
dc.contributor.otherUAM. Departamento de Medicinaes_ES
dc.contributor.otherInstituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)es_ES
dc.date.accessioned2018-03-21T16:05:13Z
dc.date.available2018-03-21T16:05:13Z
dc.date.issued2018-01-01
dc.identifier.citationBone Joint Research 7.1 (2018): 58-68es_ES
dc.identifier.issn2046-3758es_ES
dc.identifier.urihttp://hdl.handle.net/10486/681580
dc.description.abstractObjectives: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTHrelated protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. Methods: We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells. Results: We showed that both N- and C-terminal PTHrP peptides at 100 nM decreased reactive oxygen species production and forkhead box protein O activation following hydrogen peroxide (H 2 O 2 )-induced oxidation, which was related to decreased lipid oxidative damage and caspase-3 activation in these cells. This was associated with their ability to restore the deleterious effects of H 2 O 2 on cell growth and alkaline phosphatase activity, as well as on the expression of various osteoblast differentiation genes. The addition of Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2 inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal PTHrP. Conclusion: These findings indicate that the antioxidant properties of PTHrP act through its N- and C-terminal domains and provide novel insights into the osteogenic action of PTHrP.en_US
dc.description.sponsorshipThis work has been funded by grants from the Fundacion para la Investigacion Osea y Metabolismo Mineral-FEIOMM and the Instituto de Salud Carlos III (PI11/00449, PI15/00340, PI1600065, RD12/0043/0029, RD12/0043/0008 and RD12/0043/0018,). J. A. Ardua, D. Lozano, and S. Portal-Nunez are recipients of postdoctoral contracts from the Ministerio de Economia y Competitividad, Juan de la Cierva program JCI-2011-09548, FPDI-2013-17268, and RETICEF [FEDER “una manera de hacer Europa” (RD12/0043/0008)]en_US
dc.format.extent11 pag.es_ES
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherBritish Editorial Society of Bone and Joint Surgeryes_ES
dc.relation.ispartofBone Joint Researches_ES
dc.rights© 2018 Portal-Núñez et al.es_ES
dc.subject.otherAntioxidant activityen_US
dc.subject.otherOsteostatinen_US
dc.subject.otherParathyroid hormone-related proteinen_US
dc.titleParathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domainsen_US
dc.typearticleen
dc.subject.ecienciaMedicinaes_ES
dc.relation.publisherversionhttps://doi.org/10.1302/2046-3758.71.BJR-2016-0242.R2es_ES
dc.identifier.doi10.1302/2046-3758.71.BJR-2016-0242.R2es_ES
dc.identifier.publicationfirstpage58es_ES
dc.identifier.publicationissue1es_ES
dc.identifier.publicationlastpage68es_ES
dc.identifier.publicationvolume7es_ES
dc.relation.projectIDGobierno de España. PI11/00449es_ES
dc.relation.projectIDGobierno de España. PI15/00340es_ES
dc.relation.projectIDGobierno de España. PI1600065es_ES
dc.relation.projectIDGobierno de España. RD12/0043/0029es_ES
dc.relation.projectIDGobierno de España. RD12/0043/0008es_ES
dc.relation.projectIDGobierno de España. RD12/0043/0018es_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.rights.ccReconocimiento – NoComerciales_ES
dc.rights.accessRightsopenAccessen
dc.authorUAMHerrero-Beaumont Cuenca, Gabriel (259891)
dc.facultadUAMFacultad de Medicina
dc.institutoUAMInstituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD)


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