title: Advanced glycation end products in degenerative nucleus pulposus with diabetes.
abstract: Diabetes mellitus (DM) has been clinically proved as a risk factor of disc degeneration, and the accumulation of advanced glycation end products (AGEs) is known to be potentially involved in diabetes. The purpose of this study is to investigate the effect of AGEs in the degeneration process of diabetic nucleus pulposus (NP) in rats and humans. Diabetic NP cells from rat coccygeal discs were treated with different concentrations of AGEs (0, 50, and 100 µg/ml) for 3 days, and mRNA expressions of MMP-2 and RAGE were measured by real-time RT-PCR. In addition, conditioned medium from NP cells was used to analyze protein expression of MMP-2 activity and ERK by gelatin zymography and Western blot. These experiments were repeated using human intervertebral disc samples. The immunohistochemical expression of AGEs was significantly increased in diabetic discs. In response to AGEs, an increase of MMP-2, RAGE, and ERK at both mRNA and protein expression levels was observed in diabetic NP cells. The findings suggest that AGEs and DM are associated with disc degeneration in both species. Hyperglycemia in diabetes enhances the accumulation of AGEs in the NP and triggers disc degeneration.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259 Wenhwa 1st Road, Taoyuan, Taiwan, R.O.C.; Department of Orthopaedic Surgery, Spine Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
authors.forename: Tsung-Ting
authors.initials: TT
authors.lastname: Tsai
authors.forename: Natalie Yi-Ju
authors.initials: NY
authors.lastname: Ho
authors.forename: Ying-Ting
authors.initials: YT
authors.lastname: Lin
authors.forename: Po-Liang
authors.initials: PL
authors.lastname: Lai
authors.forename: Tsai-Sheng
authors.initials: TS
authors.lastname: Fu
authors.forename: Chi-Chien
authors.initials: CC
authors.lastname: Niu
authors.forename: Lih-Huei
authors.initials: LH
authors.lastname: Chen
authors.forename: Wen-Jer
authors.initials: WJ
authors.lastname: Chen
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007403:Intervertebral Disc / Q000187:drug effects*; D055959:Intervertebral Disc Degeneration / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2
keywords: advanced glycation end products; diabetes mellitus; disc degeneration; glucose