Advanced glycation endproducts interefere 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 (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 beta-peptide (conserved sequence 113-125 of the beta subunit of integrins) or with two other peptides, RGD (Arg-Gly-Asp) and DGEA (Asp-Gly-Glu-Ala), which are recognition sequences for the alpha-subunits of alpha(1,5)beta(1) and alpha(2)beta(1) integrins. Collagen glycation inhibited the adhesion of UMR106 osteoblasts to the matrix (40% reduction versus Col, P > 0.001). beta-Peptide showed a dose- and glycation-dependent inhibitory effect on adhesion, and at a concentration of 100 microM decreased the attachment of UMR106 cells to both matrices (42% to Col, P<0.001and 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. beta-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 alpha and beta integrin subunits participate in osteoblastic attachment to type-I collagen, probably through the alpha(1,5)beta(1) and alpha(2)beta(1) 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.
Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, (1900) La Plata, Argentina.
Antonio Desmond
AD
McCarthy
Toshimasa
T
Uemura
Susana Beatriz
SB
Etcheverry
Ana María
AM
Cortizo
D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D039001:Integrin alpha Chains / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D051381:Rats
D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016023:Integrins; D010455:Peptides