Pentosidine effects on human osteoblasts in vitro.
Osteoporosis, a multifactorial and progressive skeletal metabolic disease, is characterized by low-mass density and structural deterioration of bone micro-architecture that leads to enhanced bone fragility and increased susceptibility to fractures. Recently, it has been proposed that age-related bone loss could be correlated with the glycoxidative process. The aim of the present study was to investigate the in vitro effects of pentosidine, a glycoxidative end product, on human osteoblasts (HOb). The mineralization rate, the specific bone markers (alkaline phosphatase [ALP], collagen Ialpha1 [COL Ialpha1], osteocalcin [BGP]), and the human receptor for advanced glycation end products (RAGE) gene expression have been evaluated. Pentosidine incubation of HOb caused a significant decrease in ALP, Col Ialpha1, and RAGE mRNA levels, but only the RAGE gene expression decreased with no dose dependency. Moreover, pentosidine incubation of osteoblasts hampered the formation of bone nodules. No effect was observed on BGP gene expression under all experimental conditions. Our data gives further support to a detrimental effect of AGEs on bone that leads to functional alterations of osteoblasts. This study addresses a crucial role of protein glycoxidation in the bone mineralization process. AGEs formation and accumulation in bone may be one of the first pathogenetic steps of bone remodeling in aging and in age-related diseases, leading to enhanced bone mass loss.
Sanguineti
Roberta
R
Division of Geriatrics, Deptartment of Internal Medicine and Medical Specialities, University of Genoa, Genoa, Italy.
Storace
Daniela
D
Monacelli
Fiammetta
F
Federici
Alberto
A
Odetti
Patrizio
P
D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019637:Orthopedic Procedures; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015675:Osteocalcin / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D015675:Osteocalcin; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D008239:Lysine