Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

Diabetics have an increased prevalence of periodontitis, and diabetes is one of thecausative factors of severe periodontitis. Apoptosis is thought to be involved inthis pathogenic relationship. The aim of this study was to investigate apoptosis inhuman periodontal ligament (PDL) fibroblasts induced by advanced glycation endproducts (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs,and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblaststhat were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serumalbumin (BSA) alone, or given no treatment (control). Microscopy and real-timequantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformedand expressed higher levels of RAGE and caspase 3. Cell viability assays and flowcytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) andincreased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining andterminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed thatAGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed thatthe changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGEparticipates in and exacerbates periodontium destruction.