Genome-wide Analyses of Gene Expression Profile Identify Key Genes and Pathways Involved in Skeletal Response to Phosphate and 1,25-dihydroxyvitamin D in Vivo

Overview

Journal J Steroid Biochem Mol Biol

Specialties Biochemistry
Molecular Biology

Date 2023 May 28

PMID 37245694

Authors

Seong Min Lee

Mark B Meyer

Nancy A Benkusky

J Wesley Pike

Affiliations

Soon will be listed here.

Abstract

Phosphate (P) is an essential element involved in various biological actions, such as bone integrity, energy production, cell signaling and molecular component. P homeostasis is modulated by 4 main tissues; intestine, kidney, bone, and parathyroid gland, where 1,25-dihydroxyvitamin D (1,25(OH)D), parathyroid hormone and fibroblast growth factor 23 (FGF23) are produced and/or have an influence. In bone, serum P level modulates the production of FGF23 which then controls not only P excretion but also vitamin D metabolism in kidney in an endocrine manner. The hormonally active form of vitamin D, 1,25(OH)D, also has a significant effect on skeletal cells via its receptor, the vitamin D receptor, to control gene expression which mediates bone metabolism as well as mineral homeostasis. In this study, we adopted RNA-seq analysis to understand genome-wide skeletal gene expression regulation in response to P and 1,25(OH)D. We examined lumbar 5 vertebrae from the mice that were fed P deficient diet for a week followed by an acute high P diet for 3, 6, and 24 h as well as mice treated with 1,25(OH)D intraperitoneally for 6 h. Further identification and exploration of the genes regulated by P and 1,25(OH)D showed that P dynamically modulates the expression of skeletal genes involved in various biological processes while 1,25(OH)D regulates genes highly related to bone metabolism. Our in vivo data were then compared with in vitro data that we previously obtained, which suggests that the gene expression profiles presented in this report mainly represent those of osteocytes. Interestingly, it was found that even though the skeletal response to P is distinguished from that to 1,25(OH)D, both factors have an effect on Wnt signaling pathway to modulate bone homeostasis. Taken together, this report presents genome-wide data that provide a foundation to understand molecular mechanisms by which skeletal cells respond to P and 1,25(OH)D.

Citing Articles

Molecular insights into mineralotropic hormone inter-regulation.

Pike J, Lee S, Meyer M Front Endocrinol (Lausanne). 2023; 14:1213361.

PMID: 37441497 PMC: 10334211. DOI: 10.3389/fendo.2023.1213361.

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