Effects of high glucose and high insulin concentrations on osteoblast function in vitro

Página do item simplificado
dc.contributor.authorCunha, Juliana S. [UNIFESP]
dc.contributor.authorFerreira, Vanessa M. [UNIFESP]
dc.contributor.authorMaquigussa, Edgar [UNIFESP]
dc.contributor.authorNaves, Marcelo A. [UNIFESP]
dc.contributor.authorBoim, Mirian A. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:37:55Z
dc.date.available2016-01-24T14:37:55Z
dc.date.issued2014-10-01
dc.description.abstractBone disease as a consequence of diabetes mellitus (DM) is not fully understood. the effects of high glucose (30 mM), high insulin (50 nM), or mannitol (30 mM; osmotic control) were evaluated on MC3T3-E1 cells (osteoblasts) in vitro. the mRNA and protein levels of parathyroid hormone (PTH) receptor (PTH1R), collagen I, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), and glucose transporter (GLUT1) were estimated by real-time polymerase chain reaction or Western blotting. the mineralization capacity was analyzed by von Kossa staining. High glucose induced overexpression of RANKL (2x) and OPG (30x), suggesting that RANKL-induced osteoclast activity might not be a dominant mechanism of bone disease in DM, since this increase was followed by increased OPG. Collagen I increased by 12x, indicating an excess of organic matrix production. the expression of ALP decreased by 50 %, indicating a deficit in mineralization capacity, confirmed by von Kossa staining. Mannitol induced similar effects as glucose suggesting that extracellular hyperosmolarity was able to stimulate organic matrix production. GLUT1 expression was not altered, and insulin did not reverse most of the effects of glucose, suggesting that glucose uptake by osteoblasts was not altered by high glucose. the data suggest that the bone fragility typical of DM is not a consequence of excessive bone reabsorption but is instead attributable to a defect in organic matrix mineralization. the heightened increase in OPG versus RANKL might cause a decrease in the bone-remodeling cycle. Osteoblasts appear to be more sensitive to extracellular hypertonicity than to the intracellular metabolic effects of hyperglycemia.en
dc.description.affiliationUniversidade Federal de São Paulo, Div Renal, Dept Med, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, BR-04023900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Renal, Dept Med, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, BR-04023900 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundacao Oswaldo Ramos (FOR)
dc.format.extent249-256
dc.identifierhttp://dx.doi.org/10.1007/s00441-014-1913-x
dc.identifier.citationCell and Tissue Research. New York: Springer, v. 358, n. 1, p. 249-256, 2014.
dc.identifier.doi10.1007/s00441-014-1913-x
dc.identifier.issn0302-766X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38266
dc.identifier.wosWOS:000343044300021
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofCell and Tissue Research
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.subjectOsteoblasten
dc.subjectDiabetes mellitusen
dc.subjectGlucoseen
dc.subjectInsulinen
dc.subjectMineralizationen
dc.subjectMouse cell lineen
dc.titleEffects of high glucose and high insulin concentrations on osteoblast function in vitroen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
Em verificação - Geral