Skip to main content
Top
Published in: Archives of Gynecology and Obstetrics 5/2012

Open Access 01-05-2012 | General Gynecology

Up-regulation of inhibitors of DNA binding/differentiation gene during alendronate-induced osteoblast differentiation

Authors: Ae Ra Kang, Young Rim Oh, Heung Yeol Kim, Min Jung Park, Bo Sun Joo, Won Jun Choi, Ji Young Lee, Min Hyung Jung, Yong Il Ji, Jong Soon Choi

Published in: Archives of Gynecology and Obstetrics | Issue 5/2012

Login to get access

Abstract

Purpose

To investigate the effect of alendronate on the expression of Id genes in osteoblast differentiation.

Methods

C2C12 cells were treated with alendronate for various concentrations and time periods. For evaluation of alendronate-induced osteoblast differentiation in C2C12 cells, alkaline phosphatase (ALP) activity was measured. The expression of osteoblast differentiation markers such as ALP, type-1 collagen (Col 1), and osteocalcin (OCN), and the expression of Id-1 and Id-2 were measured by RT-PCR. In order to understand the mechanism underlying the regulation of Id genes, the promoter region of the Id-1 gene was identified. Database analysis of the promoter region for Id-1 using known consensus sequences identified several putative response elements, including CCAAT/enhancer-binding protein beta (C/EBPβ).

Results

Alendronate treatment significantly increased not only ALP activity but also the expression of ALP, Col 1, and OCN, Id-1 and Id-2. C/EBPβ and alendronate cooperatively increased the promoter activity and expression of Id-1.

Conclusions

These results suggest that C/EBPβ-mediated Id-1 transcriptional activation may regulate alendronate-induced osteoblast differentiation of C2C12 cells.
Literature
2.
go back to reference Garcia-Moreno C, Serrano S, Nacher M, Farre M, Diez A, Marinoso ML, Carbonell J, Mellibovsky L, Nogues X, Ballester J, Aubia J (1998) Effect of alendronate on cultured normal human osteoblasts. Bone 22(3):233–239PubMedCrossRef Garcia-Moreno C, Serrano S, Nacher M, Farre M, Diez A, Marinoso ML, Carbonell J, Mellibovsky L, Nogues X, Ballester J, Aubia J (1998) Effect of alendronate on cultured normal human osteoblasts. Bone 22(3):233–239PubMedCrossRef
3.
go back to reference Reinholz GG, Getz B, Pederson L, Sanders ES, Subramaniam M, Ingle JN, Spelsberg TC (2000) Bisphosphonates directly regulate cell proliferation, differentiation, and gene expression in human osteoblasts. Cancer Res 60(21):6001–6007PubMed Reinholz GG, Getz B, Pederson L, Sanders ES, Subramaniam M, Ingle JN, Spelsberg TC (2000) Bisphosphonates directly regulate cell proliferation, differentiation, and gene expression in human osteoblasts. Cancer Res 60(21):6001–6007PubMed
4.
go back to reference Im GI, Qureshi SA, Kenney J, Rubash HE, Shanbhag AS (2004) Osteoblast proliferation and maturation by bisphosphonates. Biomaterials 25(18):4105–4115PubMedCrossRef Im GI, Qureshi SA, Kenney J, Rubash HE, Shanbhag AS (2004) Osteoblast proliferation and maturation by bisphosphonates. Biomaterials 25(18):4105–4115PubMedCrossRef
5.
go back to reference Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T (1999) Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104(10):1363–1374PubMedCrossRef Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T (1999) Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104(10):1363–1374PubMedCrossRef
6.
go back to reference Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T (1994) Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 127(6 Pt 1):1755–1766PubMedCrossRef Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T (1994) Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 127(6 Pt 1):1755–1766PubMedCrossRef
8.
go back to reference Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24(2):218–235PubMedCrossRef Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24(2):218–235PubMedCrossRef
9.
go back to reference Malaval L, Liu F, Roche P, Aubin JE (1999) Kinetics of osteoprogenitor proliferation and osteoblast differentiation in vitro. J Cell Biochem 74(4):616–627PubMedCrossRef Malaval L, Liu F, Roche P, Aubin JE (1999) Kinetics of osteoprogenitor proliferation and osteoblast differentiation in vitro. J Cell Biochem 74(4):616–627PubMedCrossRef
10.
go back to reference Fu L, Tang T, Miao Y, Zhang S, Qu Z, Dai K (2008) Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. Bone 43(1):40–47PubMedCrossRef Fu L, Tang T, Miao Y, Zhang S, Qu Z, Dai K (2008) Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. Bone 43(1):40–47PubMedCrossRef
11.
go back to reference Xiong Y, Yang HJ, Feng J, Shi ZL, Wu LD (2009) Effects of alendronate on the proliferation and osteogenic differentiation of MG-63 cells. J Int Med Res 37(2):407–416PubMed Xiong Y, Yang HJ, Feng J, Shi ZL, Wu LD (2009) Effects of alendronate on the proliferation and osteogenic differentiation of MG-63 cells. J Int Med Res 37(2):407–416PubMed
12.
go back to reference Peng Y, Kang Q, Luo Q, Jiang W, Si W, Liu BA, Luu HH, Park JK, Li X, Luo J, Montag AG, Haydon RC, He TC (2004) Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells. J Biol Chem 279(31):32941–32949PubMedCrossRef Peng Y, Kang Q, Luo Q, Jiang W, Si W, Liu BA, Luu HH, Park JK, Li X, Luo J, Montag AG, Haydon RC, He TC (2004) Inhibitor of DNA binding/differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells. J Biol Chem 279(31):32941–32949PubMedCrossRef
13.
go back to reference Maeda Y, Tsuji K, Nifuji A, Noda M (2004) Inhibitory helix-loop-helix transcription factors Id1/Id3 promote bone formation in vivo. J Cell Biochem 93(2):337–344PubMedCrossRef Maeda Y, Tsuji K, Nifuji A, Noda M (2004) Inhibitory helix-loop-helix transcription factors Id1/Id3 promote bone formation in vivo. J Cell Biochem 93(2):337–344PubMedCrossRef
15.
go back to reference Tominaga H, Maeda S, Hayashi M, Takeda S, Akira S, Komiya S, Nakamura T, Akiyama H, Imamura T (2008) CCAAT/enhancer-binding protein beta promotes osteoblast differentiation by enhancing Runx2 activity with ATF4. Mol Biol Cell 19(12):5373–5386PubMedCrossRef Tominaga H, Maeda S, Hayashi M, Takeda S, Akira S, Komiya S, Nakamura T, Akiyama H, Imamura T (2008) CCAAT/enhancer-binding protein beta promotes osteoblast differentiation by enhancing Runx2 activity with ATF4. Mol Biol Cell 19(12):5373–5386PubMedCrossRef
16.
go back to reference Kreider BL, Benezra R, Rovera G, Kadesch T (1992) Inhibition of myeloid differentiation by the helix–loop–helix protein Id. Science 255(5052):1700–1702PubMedCrossRef Kreider BL, Benezra R, Rovera G, Kadesch T (1992) Inhibition of myeloid differentiation by the helix–loop–helix protein Id. Science 255(5052):1700–1702PubMedCrossRef
17.
go back to reference Ruzinova MB, Benezra R (2003) Id proteins in development, cell cycle and cancer. Trends Cell Biol 13(8):410–418PubMedCrossRef Ruzinova MB, Benezra R (2003) Id proteins in development, cell cycle and cancer. Trends Cell Biol 13(8):410–418PubMedCrossRef
18.
go back to reference Lopez-Rovira T, Chalaux E, Massague J, Rosa JL, Ventura F (2002) Direct binding of Smad1 and Smad4 to two distinct motifs mediates bone morphogenetic protein-specific transcriptional activation of Id1 gene. J Biol Chem 277(5):3176–3185PubMedCrossRef Lopez-Rovira T, Chalaux E, Massague J, Rosa JL, Ventura F (2002) Direct binding of Smad1 and Smad4 to two distinct motifs mediates bone morphogenetic protein-specific transcriptional activation of Id1 gene. J Biol Chem 277(5):3176–3185PubMedCrossRef
19.
go back to reference Korchynskyi O, ten Dijke P (2002) Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J Biol Chem 277(7):4883–4891PubMedCrossRef Korchynskyi O, ten Dijke P (2002) Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J Biol Chem 277(7):4883–4891PubMedCrossRef
20.
go back to reference Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA (1991) Bisphosphonate action Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 88(6):2095–2105PubMedCrossRef Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA (1991) Bisphosphonate action Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 88(6):2095–2105PubMedCrossRef
21.
go back to reference Klein BY, Ben-Bassat H, Breuer E, Solomon V, Golomb G (1998) Structurally different bisphosphonates exert opposing effects on alkaline phosphatase and mineralization in marrow osteoprogenitors. J Cell Biochem 68(2):186–194PubMedCrossRef Klein BY, Ben-Bassat H, Breuer E, Solomon V, Golomb G (1998) Structurally different bisphosphonates exert opposing effects on alkaline phosphatase and mineralization in marrow osteoprogenitors. J Cell Biochem 68(2):186–194PubMedCrossRef
22.
go back to reference Sama AA, Khan SN, Myers ER, Huang RC, Cammisa FP Jr, Sandhu HS, Lane JM (2004) High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model. Clin Orthop Relat Res 425:135–142PubMedCrossRef Sama AA, Khan SN, Myers ER, Huang RC, Cammisa FP Jr, Sandhu HS, Lane JM (2004) High-dose alendronate uncouples osteoclast and osteoblast function: a study in a rat spine pseudarthrosis model. Clin Orthop Relat Res 425:135–142PubMedCrossRef
23.
go back to reference Nakashima A, Katagiri T, Tamura M (2005) Cross-talk between Wnt and bone morphogenetic protein 2 (BMP-2) signaling in differentiation pathway of C2C12 myoblasts. J Biol Chem 280(45):37660–37668PubMedCrossRef Nakashima A, Katagiri T, Tamura M (2005) Cross-talk between Wnt and bone morphogenetic protein 2 (BMP-2) signaling in differentiation pathway of C2C12 myoblasts. J Biol Chem 280(45):37660–37668PubMedCrossRef
Metadata
Title
Up-regulation of inhibitors of DNA binding/differentiation gene during alendronate-induced osteoblast differentiation
Authors
Ae Ra Kang
Young Rim Oh
Heung Yeol Kim
Min Jung Park
Bo Sun Joo
Won Jun Choi
Ji Young Lee
Min Hyung Jung
Yong Il Ji
Jong Soon Choi
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Archives of Gynecology and Obstetrics / Issue 5/2012
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-011-2141-1

Other articles of this Issue 5/2012

Archives of Gynecology and Obstetrics 5/2012 Go to the issue