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Inhibition of the canonical Wnt pathway by high glucose can be reversed by parathyroid hormone-related protein in osteoblastic cells

López-Herradón, Ana ; Portal-Núñez, Sergio ; García-Martín, Adela ; Lozano, Daniel ; Pérez-Martínez, Francisco C. ; Ceña, Valentín ; Esbrit, Pedro

Journal of cellular biochemistry, 2013-08, Vol.114 (8), p.1908-1916 [Periódico revisado por pares]

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Título:
Inhibition of the canonical Wnt pathway by high glucose can be reversed by parathyroid hormone-related protein in osteoblastic cells
Autor: López-Herradón, Ana ; Portal-Núñez, Sergio ; García-Martín, Adela ; Lozano, Daniel ; Pérez-Martínez, Francisco C. ; Ceña, Valentín ; Esbrit, Pedro
Assuntos: Animals ; Antimanic Agents - pharmacology ; beta Catenin - genetics ; beta Catenin - metabolism ; CANONICAL Wnt PATHWAY ; Cell Line ; Glucose - genetics ; Glucose - metabolism ; HIGH GLUCOSE ; Humans ; Lithium Chloride - pharmacology ; Low Density Lipoprotein Receptor-Related Protein-5 - genetics ; Low Density Lipoprotein Receptor-Related Protein-5 - metabolism ; Low Density Lipoprotein Receptor-Related Protein-6 - genetics ; Low Density Lipoprotein Receptor-Related Protein-6 - metabolism ; Mice ; Mutation ; OSTEOBLASTS ; Osteoblasts - cytology ; Osteoblasts - metabolism ; Osteogenesis - drug effects ; Osteogenesis - genetics ; Parathyroid Hormone-Related Protein - metabolism ; Parathyroid Hormone-Related Protein - pharmacology ; Protein Stability ; PTHrP ; Wnt Signaling Pathway - drug effects ; Wnt Signaling Pathway - physiology ; Wnt3A Protein - metabolism ; Wnt3A Protein - pharmacology
É parte de: Journal of cellular biochemistry, 2013-08, Vol.114 (8), p.1908-1916
Notas: Comunidad Autónoma de Madrid - No. S-2009/Mat-1472
Spanish Ministerio de Educación y Cultura - No. SAF2005-05254
Fundación de Investigación Médica Mutua Madrileña
Consejería de Educación de la Junta de Castilla-La Mancha (JCCM) - No. POII10-0274-3182
ark:/67375/WNG-8MSK817F-7
Spanish Ministerio de Ciencia e Innovación (MICINN)-Juan de la Cierva program - No. JCI-2009-04360
Fundación Conchita Rábago and Ministerio de Educación-FPU program - No. AP2009-1871
ArticleID:JCB24535
The authors have declared that no competing interests exist.
istex:E40CE8802690CD279C6FFDC672197BB3FD63503D
Fundación Española de Investigación Ósea y del Metabolismo Mineral (FEIOMM)
Instituto de Salud Carlos III - No. PI050117; No. PI080922; No. PI11/00449, RD06/0013/1002, and RD12/0043/0008
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Descrição: Recent in vivo findings suggest that the bone sparing effect of parathyroid hormone‐related protein (PTHrP) in diabetic mice might occur at least in part through targeting a suppressed Wnt/β‐catenin pathway in osteoblasts. We here aimed to examine the inhibitory action of a high glucose environment on specific components of the canonical Wnt pathway, and the putative compensatory effects of PTHrP, in osteoblastic cell cultures. Mouse osteoblastic MC3T3‐E1 cells and primary cultures of fetal mouse calvaria were exposed to normal (5.5 mM) or high (25 mM) D‐glucose (HG), with or without PTHrP (1–36) or PTHrP (107–139) for different times. In some experiments, MC3T3‐E1 cells were incubated with the Wnt pathway activators Wnt3a and LiCl, or were transfected with plasmids encoding either a mutated β‐catenin that cannot be targeted for degradation or a human PTHrP (−36/+139) cDNA, or the corresponding empty plasmid, in the presence or absence of HG. The gene expression of Wnt3a and low density receptor‐like proteins (LRP)‐5 and 6, as well as β‐catenin protein stabilization and β‐catenin‐dependent transcription activity were evaluated. Oxidative stress status under HG condition was also assessed. The present data demonstrate that HG can target different components of the canonical Wnt pathway, while β‐catenin degradation appears to be a key event leading to inhibition of Wnt/β‐catenin signaling in mouse osteoblastic cells. Both PTHrP peptides tested were able to counteract this deleterious action of HG. These in vitro findings also provide new clues to understand the underlying mechanisms whereby PTHrP can increase bone formation. J. Cell. Biochem. 114: 1908–1916, 2013. © 2013 Wiley Periodicals, Inc.
Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Idioma: Inglês

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Inhibition of the canonical Wnt pathway by high glucose can be reversed by parathyroid hormone-related protein in osteoblastic cells

López-Herradón, Ana ; Portal-Núñez, Sergio ; García-Martín, Adela ; Lozano, Daniel ; Pérez-Martínez, Francisco C. ; Ceña, Valentín ; Esbrit, Pedro

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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