|
KMID : 1007020080060020079
|
|
Korean Soceity of Osteroporosis
2008 Volume.6 No. 2 p.79 ~ p.86
|
|
|
Study on the Mechanism of Action of Bisphosphonate in Osteoblast Differentiatin
|
|
Kim Heung-Yeol
Eo Wan-Kyu
Oh Young-Rim
|
|
|
Abstract
|
|
|
Objectives: Alendronate is a representative third generation bisphosphonates that is widely used in clinical treatment of various metabolic bone diseases and the primary action is the inhibition of osteoclastic bone resorption. Some studies suggest a possible role of bisphosphonates in osteoblastic activity. However, little is known about the mechanism of action of alendronate in osteoblast formation and differentiation has not yet been clearly elucidated. Therefore, this study was aimed to investigate the effect of alendronate on osteoblast proliferation and differentiation.
Methods: The expression of genes for ALP, osteocalcin (OCN), collagen I α1 (Col 1), inhibitor of differentiation (Id) and cathepsin K (CTSK) were examined by RT-PCR method. Transcription factors related to the increased expression of Id genes were identified with TRANSFEC program. The effect of these transcription factors on the expression of Id genes were tested by promoter assay.
Results: Expressions of ALP, Col 1 and OCN genes had a tendency to increase with decreasing of alendronate concentrations before 24 hours of treatment in both cell lines. The expression of Id-1 gene began to increase from 10-6 M of alendronate compared to the control group and kept to 10-8 M. However, Id-2 gene expression was increased gradually with increasing of alendronate concentrations. Among transcription factors related to the promoter of Id genes, CREB and C/EBPβ increased promoter activity of Id genes to 2-fold and 4-fold, respectively. Co-treatment of C/EBPβ and alendronate resulted in a significant increased promoter activity of Id genes compared to each single treatment.
Conclusion: This study shows that alendronate may be associated with the increased expression of Id genes via a synergistic interaction with C/EBPβ.
|
|
|
KEYWORD
|
|
|
Bisphosphonate, Osteococlost, Id genes
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|