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Identification of a novel parathyroid hormone-responsive gene in human osteoblastic cells
A E Adams1, M Rosenblatt, L J Suva
1Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Institute of Medicine and Harvard Medical School, Boston, MA 02215, USA. aadams@bidmc.harvard.edu
Abstract:
Parathyroid hormone (PTH) is a potent stimulator of osteoblastic cell function in vitro and bone resorption and formation in vivo; however, the details of the molecular mechanism(s) responsible for PTH action and the regulation of gene expression in response to PTH remain unknown. In this study, we employed an mRNA differential display (DRD) approach to examine the initial events in gene expression in human osteoblast-like SaoS-2/B10 cells exposed to 10(-7) mol/L bPTH(1-34). This approach identified several differentially regulated mRNA species, including a novel paired-class homeobox protein, osteoblast-specific factor-2 (OSF-2), and a unique clone with no known sequence homology (clone G18). G18 is a previously unidentified human gene, expressed in a wide variety of human tissues, including heart, brain, placenta, skeletal muscle, and kidney, and is regulated by PTH in osteoblastic cells in vitro. This mRNA appears to be the product of a single gene, which is alternatively spliced to produce multiple transcript sizes observed in several tissues, except bone and bone-derived cells, in which a single predominant approximately 1.8 kb transcript is observed. Our study has identified several genes that have expression altered significantly by treatment with bPTH(1-34), and which may provide insight into the immediate effects of PTH on osteoblast-like cells and ultimately on the mechanism of action and bioactivity of PTH.
Insights
Parathyroid hormone (PTH) regulates gene expression in bone cells. This study identified novel genes, including OSF-2 and G18, affected by PTH, offering insights into bone remodeling mechanisms.
Area of Science:
- Molecular Biology
- Endocrinology
- Bone Biology
Background:
- Parathyroid hormone (PTH) influences bone metabolism, but its molecular mechanisms and gene regulation effects are not fully understood.
- Osteoblastic cells are crucial for bone formation and resorption, responding to hormonal signals like PTH.
Purpose of the Study:
- To investigate the immediate gene expression changes in human osteoblast-like cells stimulated by PTH.
- To identify novel genes regulated by PTH in the context of bone cell function.
Main Methods:
- Utilized mRNA differential display (DRD) to analyze gene expression in SaoS-2/B10 cells treated with bPTH(1-34).
- Identified differentially expressed mRNA species, including novel genes and known proteins.
Main Results:
- Identified osteoblast-specific factor-2 (OSF-2) and a novel gene, G18, as significantly regulated by PTH.
- G18 is expressed in various human tissues and shows alternative splicing, with a predominant 1.8 kb transcript in bone cells.
- Several other genes were found to be differentially expressed following bPTH(1-34) treatment.
Conclusions:
- PTH significantly alters gene expression in osteoblast-like cells, revealing immediate molecular responses.
- The identified genes, OSF-2 and G18, may play roles in PTH's mechanism of action and bioactivity in bone.
- This study provides a foundation for understanding PTH-mediated gene regulation in bone biology.