Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains

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dc.contributor.author Portal-Núñez, Sergio
dc.contributor.author Ardura, J. A.
dc.contributor.author Lozano, D.
dc.contributor.author Martínez de Toda, I.
dc.contributor.author De La Fuente, M.
dc.contributor.author Herrero-Beaumont, Gabriel
dc.contributor.author Largo, R.
dc.contributor.author Esbrit, P.
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.contributor.other Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) es_ES
dc.date.accessioned 2018-03-21T16:05:13Z
dc.date.available 2018-03-21T16:05:13Z
dc.date.issued 2018-01-01
dc.identifier.citation Bone Joint Research 7.1 (2018): 58-68 es_ES
dc.identifier.issn 2046-3758 es_ES
dc.identifier.uri http://hdl.handle.net/10486/681580
dc.description.abstract Objectives: 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.sponsorship This 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.extent 11 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher British Editorial Society of Bone and Joint Surgery es_ES
dc.relation.ispartof Bone Joint Research es_ES
dc.rights © 2018 Portal-Núñez et al. es_ES
dc.subject.other Antioxidant activity en_US
dc.subject.other Osteostatin en_US
dc.subject.other Parathyroid hormone-related protein en_US
dc.title Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/10.1302/2046-3758.71.BJR-2016-0242.R2 es_ES
dc.identifier.doi 10.1302/2046-3758.71.BJR-2016-0242.R2 es_ES
dc.identifier.publicationfirstpage 58 es_ES
dc.identifier.publicationissue 1 es_ES
dc.identifier.publicationlastpage 68 es_ES
dc.identifier.publicationvolume 7 es_ES
dc.relation.projectID Gobierno de España. PI11/00449 es_ES
dc.relation.projectID Gobierno de España. PI15/00340 es_ES
dc.relation.projectID Gobierno de España. PI1600065 es_ES
dc.relation.projectID Gobierno de España. RD12/0043/0029 es_ES
dc.relation.projectID Gobierno de España. RD12/0043/0008 es_ES
dc.relation.projectID Gobierno de España. RD12/0043/0018 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento – NoComercial es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Herrero-Beaumont Cuenca, Gabriel (259891)


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