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

• Autores: McCarthy, Antonio Desmond; Uemura, Toshimasa; Etcheverry, Susana Beatriz; Cortizo, Ana María
• Año de publicación: 2004
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ADVANCED GLYCATION ENDPRODUCTS; AGES; ARG-GLY-ASP; ASP-GLY-GLU-ALA; DGEA; DMEM; DULBECCO'S MODIFIED EAGLE'S MEDIUM; ECM; EDTA; ETHYLENEDIAMINO-TETRA-ACETIC ACID; EXTRACELLULAR MATRIX; FBS; FETAL BOVINE SERUM; PBS; PHOSPHATE BUFFERED SALINE SOLUTION; RGD
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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 α1,5β1 and α2β1 integrins. Collagen glycation inhibited the adhesion of UMR106 osteoblasts to the matrix (40% reduction versus Col, P<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, P<0.001; and 25% to AGEs-Col, P<0.01). The synthetic peptides RGD (1mM) and DGEA (5mM) inhibited the attachment of UMR106 cells to Col (30 and 20%, P<0.01 and P<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 α 1,5β1 and α2β1 integrins. 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.
Fil: McCarthy, Antonio Desmond. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra Bioquímica Patológica; Argentina
Fil: Uemura, Toshimasa. National Institute of Advanced Industrial Science and Technology; Japón
Fil: Etcheverry, Susana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra Bioquímica Patológica; Argentina
Fil: Cortizo, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra Bioquímica Patológica; Argentina