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Role of activator protein 1 transcriptional activity in the regulation of gene expression by transforming growth factor beta1 and bone morphogenetic protein 2 in ROS 17/2.8 osteoblast-like cells.
J Bone Miner Res. 2000 Dec; 15(12):2352-61.JB

Abstract

In osteoblastic cells, transforming growth factor beta1 (TGF-beta1) has been found to regulate the expression of a variety of proto-oncogenes including c-fos, c-jun, and junB. The c-fos in particular has been implicated in the mitogenic effect of TGF-beta1. Here, we examined the role of these early response genes in the regulation of osteoblast (OB) gene expression by two members of the TGF-beta superfamily, TGF-beta1 and bone morphogenetic protein 2 (BMP-2). In ROS 17/2.8 cells, TGF-beta1 as well as BMP-2 up-regulated the expression of junB and c-fos messenger RNAs (mRNAs), and this increase was correlated in both cases with an increase in activator protein 1 (AP-1) DNA-binding activity involving JunB and c-Fos proteins. Protein kinase C (PKC)- and protein tyrosine kinase (PTK)-dependent pathways have been implicated in both TGF-beta1 signaling and AP-1 gene regulation. Therefore, using the kinase inhibitors chelerythrine chloride and genistein, we showed that PKC and PTK activities, respectively, participated in TGF-beta1- and BMP-2-induced increases in junB mRNA levels. Similarly, these kinase activities were involved in the stimulatory effect of BMP-2 on c-fos mRNA expression. Using a natural dominant negative for AP-1 transcriptional activity in ROS 17/2.8 cells, we then showed that AP-1 transcription factors mediated TGF-beta1- and BMP-2-regulated expression of the (alpha1) collagen I gene as well as TGF-beta1-regulated expression of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor. Our data emphasize the role of the AP-1 transcription factor in TGF-beta1 and BMP-2 signaling and highlight the importance of this transcription factor family in the expression of OB genes.

Authors+Show Affiliations

Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11127200

Citation

Palcy, S, et al. "Role of Activator Protein 1 Transcriptional Activity in the Regulation of Gene Expression By Transforming Growth Factor Beta1 and Bone Morphogenetic Protein 2 in ROS 17/2.8 Osteoblast-like Cells." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 15, no. 12, 2000, pp. 2352-61.
Palcy S, Bolivar I, Goltzman D. Role of activator protein 1 transcriptional activity in the regulation of gene expression by transforming growth factor beta1 and bone morphogenetic protein 2 in ROS 17/2.8 osteoblast-like cells. J Bone Miner Res. 2000;15(12):2352-61.
Palcy, S., Bolivar, I., & Goltzman, D. (2000). Role of activator protein 1 transcriptional activity in the regulation of gene expression by transforming growth factor beta1 and bone morphogenetic protein 2 in ROS 17/2.8 osteoblast-like cells. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 15(12), 2352-61.
Palcy S, Bolivar I, Goltzman D. Role of Activator Protein 1 Transcriptional Activity in the Regulation of Gene Expression By Transforming Growth Factor Beta1 and Bone Morphogenetic Protein 2 in ROS 17/2.8 Osteoblast-like Cells. J Bone Miner Res. 2000;15(12):2352-61. PubMed PMID: 11127200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of activator protein 1 transcriptional activity in the regulation of gene expression by transforming growth factor beta1 and bone morphogenetic protein 2 in ROS 17/2.8 osteoblast-like cells. AU - Palcy,S, AU - Bolivar,I, AU - Goltzman,D, PY - 2000/12/29/pubmed PY - 2001/2/28/medline PY - 2000/12/29/entrez SP - 2352 EP - 61 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 15 IS - 12 N2 - In osteoblastic cells, transforming growth factor beta1 (TGF-beta1) has been found to regulate the expression of a variety of proto-oncogenes including c-fos, c-jun, and junB. The c-fos in particular has been implicated in the mitogenic effect of TGF-beta1. Here, we examined the role of these early response genes in the regulation of osteoblast (OB) gene expression by two members of the TGF-beta superfamily, TGF-beta1 and bone morphogenetic protein 2 (BMP-2). In ROS 17/2.8 cells, TGF-beta1 as well as BMP-2 up-regulated the expression of junB and c-fos messenger RNAs (mRNAs), and this increase was correlated in both cases with an increase in activator protein 1 (AP-1) DNA-binding activity involving JunB and c-Fos proteins. Protein kinase C (PKC)- and protein tyrosine kinase (PTK)-dependent pathways have been implicated in both TGF-beta1 signaling and AP-1 gene regulation. Therefore, using the kinase inhibitors chelerythrine chloride and genistein, we showed that PKC and PTK activities, respectively, participated in TGF-beta1- and BMP-2-induced increases in junB mRNA levels. Similarly, these kinase activities were involved in the stimulatory effect of BMP-2 on c-fos mRNA expression. Using a natural dominant negative for AP-1 transcriptional activity in ROS 17/2.8 cells, we then showed that AP-1 transcription factors mediated TGF-beta1- and BMP-2-regulated expression of the (alpha1) collagen I gene as well as TGF-beta1-regulated expression of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor. Our data emphasize the role of the AP-1 transcription factor in TGF-beta1 and BMP-2 signaling and highlight the importance of this transcription factor family in the expression of OB genes. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/11127200/Role_of_activator_protein_1_transcriptional_activity_in_the_regulation_of_gene_expression_by_transforming_growth_factor_beta1_and_bone_morphogenetic_protein_2_in_ROS_17/2_8_osteoblast_like_cells_ L2 - https://doi.org/10.1359/jbmr.2000.15.12.2352 DB - PRIME DP - Unbound Medicine ER -