Advanced glycation endproducts influence the mRNA expression of RAGE, RANKL and various osteoblastic genes in human osteoblasts
- 1 January 2007
- journal article
- review article
- Published by Informa UK Limited in Archives of Physiology and Biochemistry
- Vol. 113 (3), 154-161
- https://doi.org/10.1080/13813450701602523
Abstract
Glycation reactions resulting in the generation and accumulation of advanced glycation endproducts (AGEs) are potential mechanisms by which bone protein may be altered in vivo. AGEs accumulate in the bone increasingly with age come into close contact with osteoblasts or osteoclasts. The direct effect of AGEs on bone cells has not been thoroughly investigated. This study aimed to examine whether glycated bovine serum albumin (AGE – BSA) as an AGE modulate the mRNA expression of various genes in primary human osteoblast cultures. The following parameters were included: RAGE (receptor for AGEs), alkaline phosphatase, osteocalcin, osterix and RANKL (receptor activator of nuclear factor-κB ligand). Primary human osteoblast cultures were obtained from bone specimens of six patients with osteoarthrosis. Human osteoblasts were treated in AGE – BSA or control-BSA (non-glycated BSA) containing medium (5 mg/ml each) over a time course of seven days. After RT–PCR the mRNA expression was measured by real-time PCR. Related to control – BSA exposure, the mRNA expression of RAGE, RANKL and osterix increased during AGE – BSA treament. For alkaline phosphatase and osteocalcin a tendency of down-regulation was found. In summary, the study presents evidence that advanced glycation end products accumulated in bone alter osteoblasts by activation the AGE – RAGE pathway (RAGE mRNA up-regulation), inducing enhanced osteoclastogenesis (RANKL mRNA up-regulation) and impaired matrix mineralization (down-regulation of alkaline phosphatase and osteocalcin mRNA). Thus, AGEs may play a functional role in the development of bone diseases (e.g. osteoporosis).Keywords
This publication has 27 references indexed in Scilit:
- Osteoclasts: What Do They Do and How Do They Do It?The American Journal of Pathology, 2007
- Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findingsAnnals Of The Rheumatic Diseases, 2006
- Advanced glycation end products and the kidneyAmerican Journal of Physiology-Renal Physiology, 2005
- Advanced glycation end-products pentosidine and N -carboxymethyllysine are elevated in serum of patients with osteoporosisRheumatology, 2003
- Maillard reaction products in tissue proteins: New products and new perspectivesAmino Acids, 2003
- Control of osteoblast function and regulation of bone massNature, 2003
- Cytokines, Osteoprotegerin, and RANKL In Vitro and Histomorphometric Indices of Bone Turnover in Patients With Different Bone DiseasesJournal of Bone and Mineral Research, 2003
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Protein Glycation, Diabetes, and AgingRecent Progress in Hormone Research, 2001
- In vitro differentiation potential of a new human osteosarcoma cell line (HOS 58)Differentiation, 1998