Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Publisher
British Editorial Society of Bone and Joint SurgeryDate
2018-01-01Citation
10.1302/2046-3758.71.BJR-2016-0242.R2
Bone Joint Research 7.1 (2018): 58-68
ISSN
2046-3758DOI
10.1302/2046-3758.71.BJR-2016-0242.R2Funded by
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)]Project
Gobierno de España. PI11/00449; Gobierno de España. PI15/00340; Gobierno de España. PI1600065; Gobierno de España. RD12/0043/0029; Gobierno de España. RD12/0043/0008; Gobierno de España. RD12/0043/0018Editor's Version
https://doi.org/10.1302/2046-3758.71.BJR-2016-0242.R2Subjects
Antioxidant activity; Osteostatin; Parathyroid hormone-related protein; MedicinaRights
© 2018 Portal-Núñez et al.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.
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Google Scholar:Portal-Núñez, Sergio
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Ardura, J. A.
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Lozano, D.
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Martínez de Toda, I.
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De La Fuente, M.
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Herrero-Beaumont Cuenca, Gabriel
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Largo, R.
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Esbrit, P.
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