Effects of advanced glycation end products on osteoblastic cells
Date
2006
DOI
Authors
Nagao, Kiyoko
Version
OA Version
Citation
Abstract
Type 1 diabetes is associated with several pathological complications. Diabetic bone disease is one of them which consists of weak bones, low bone turnover osteopenia, and low bone density. Advanced glycation end products (AGEs) are believed to contribute to these complications which are caused by elevated serum glucose levels. However, it is not clear how AGEs cause osteopenia, which factors induce osteopenia,and what biological processes might be regulated by AGEs. The hypothesis of this research is that AGEs inhibit osteoblast function and contribute to inhibited bone healing and formation in type 1 diabetes.
To examine this hypothesis, we used N[epsilon]-(carboxymethyl) lysine modified collagen (CML-collagen) as a known AGE. We show that CML-collagen inhibits in vitro bone formation as determined by measurements of calcium deposition by primary osteoblast cultures grown on pre-coated CML-collagen or control collagen plates. The results indicated that cells grown on CML-collagen deposit less calcium compared to control-collagen. Then we carried out DNA microarray analysis in order to know which genes were regulated by growth on CML-collagen. We found that Ras oncogene family member Rab7, integrin-binding sialoprotein (bone sialoprotein 1), and dimethylarginine dimethylaminohydrolase 1 were up regulated by CML-collagen. 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMG-CoA), cartilage oligomeric matrix protein (Comp), and protocadherin beta 4 precursor were down regulated by CML-collagen.
Description
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Thesis (MSD) -- Boston University Goldman School of Dental Medicine (Orthodontics and Oral Biology)
Includes bibliographical references : leaves 54-68.
Thesis (MSD) -- Boston University Goldman School of Dental Medicine (Orthodontics and Oral Biology)
Includes bibliographical references : leaves 54-68.
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This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.