Advanced glycation endproducts interfere with integrin-mediated osteoblastic attachment to a type-I collagen matrix

The adhesion of osteoblasts to bone extracellular matrix, of which type-I collagen constitutes >85%, can modulate diverse aspects of their physiology such as growth, differentiation and mineralisation. In this study we examined the adhesion of UMR106 rat osteoblast-like cells either to a control...

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Detalles Bibliográficos
Autores: McCarthy, Antonio Desmond, Uemurab, Toshimasa, Etcheverry, Susana B., Cortizo, Ana María
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2004
País:Argentina
Institución:Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
Repositorio:CIC Digital (CICBA)
Idioma:inglés
OAI Identifier:oai:digital.cic.gba.gob.ar:11746/4897
Acceso en línea:https://digital.cic.gba.gob.ar/handle/11746/4897
Access Level:acceso abierto
Palabra clave:Ciencias Químicas
Advanced glycation endproducts
Osteoblast
Adhesion
Integrin receptors
Type-I collagen
Descripción
Sumario:The adhesion of osteoblasts to bone extracellular matrix, of which type-I collagen constitutes >85%, can modulate diverse aspects of their physiology such as growth, differentiation and mineralisation. In this study we examined the adhesion of UMR106 rat osteoblast-like cells either to a control (Col) or advanced-glycation-endproduct-modified (AGEs-Col) type I collagen matrix. We investigated the possible role of different integrin receptors in osteoblastic adhesion, by co-incubating these cells either with β-peptide (conserved sequence 113–125 of the β subunit of integrins) or with two other peptides, RGD (Arg-Gly-Asp) and DGEA (Asp-Gly-Glu-Ala), which are recognition sequences for the α-subunits of α1,5β1and α2β1integrins. Collagen glycation inhibited the adhesion of UMR106 osteoblasts to the matrix (40% reduction versus Col,<em>P</em><0.001). β-Peptide showed a dose- and glycation-dependent inhibitory effect on adhesion, and at a concentration of 100μM decreased the attachment of UMR106 cells to both matrices (42% to Col,<em>P</em><0.001; and 25% to AGEs-Col,<em>P</em><0.01). The synthetic peptides RGD (1mM) and DGEA (5mM) inhibited the attachment of UMR106 cells to Col (30 and 20%,<em>P</em><0.01 and<em>P</em><0.001, respectively), but not to AGEs-Col. β-Peptide induced an increase in UMR106 cell clumping and a decrease in cellular spreading, while DGEA increased spreading with cellular extensions in multiple directions. These results indicate that both α and β integrin subunits participate in osteoblastic attachment to type-I collagen, probably through the α1,5β1and α2β1integrins. AGEs-modification of type-I collagen impairs the integrin-mediated adhesion of osteoblastic cells to the matrix, and could thus contribute to the pathogenesis of diabetic osteopenia.