RT Journal Article
T1 Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its n-terminal and osteostatin domains
A1 Portal-Núñez, Sergio
A1 Ardura, Juan
A1 Lozano Borregón, Daniel
A1 Martínez De Toda Cabeza, Irene
A1 Fuente Del Rey, María Mónica De La
A1 Herrero-Beaumont, Gabriel
A1 Largo, Raquel
A1 Esbrit, Pedro
AB 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 (H2o2)-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 H2o2 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.
PB British Editorial Society of Bone and Joint Surgery
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/92777
UL https://hdl.handle.net/20.500.14352/92777
LA eng
NO Portal-Núñez, S., J. A. Ardura, D. Lozano, I. Martínez de Toda, M. De la Fuente, G. Herrero-Beaumont, R. Largo, and P. Esbrit. “Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains.” Bone & Joint Research 7, no. 1 (2018): 58-68. https://doi.org/10.1302/2046-3758.71.BJR-2016-0242.R2
NO European Commission
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III 
DS Docta Complutense
RD 9 abr 2025