RRC ID 61423
Author Ryynänen J, Kriebitzsch C, Meyer MB, Janssens I, Pike JW, Verlinden L, Verstuyf A.
Title Class 3 semaphorins are transcriptionally regulated by 1,25(OH)2D3 in osteoblasts.
Journal J Steroid Biochem Mol Biol
Abstract The vitamin D endocrine system is essential for calcium metabolism and skeletal integrity. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] regulates bone mineral homeostasis and acts directly on osteoblasts. In the present study we characterized the transcriptional regulation of the class 3 semaphorin (Sema3) gene family by 1,25(OH)2D3 in osteoblastic cells. Class 3 semaphorins are secreted proteins that regulate cell growth, morphology and migration, and were recently shown to be involved in bone homeostasis. In ST2, MC3T3-E1 and primary calvarial osteoblast cell cultures we found that all members of the Sema3 gene family were expressed, and that Sema3e and Sema3f were the most strongly induced 1,25(OH)2D3 target genes among the studied cell types. In addition, transcription of Sema3b and Sema3c was upregulated, whereas Sema3d and Sema3g was downregulated by 1,25(OH)2D3 in different osteoblastic cells. Chromatin immunoprecipitation analysis linked to DNA sequencing (ChIP-seq analysis) revealed the presence of the vitamin D receptor at multiple genomic loci in the proximity of Sema3 genes, demonstrating that the genes are primary 1,25(OH)2D3 targets. Furthermore, we showed that recombinant SEMA3E and SEMA3F protein were able to inhibit osteoblast proliferation. However, recombinant SEMA3s did not affect ST2 cell migration. The expression of class 3 semaphorins in osteoblasts together with their regulation by 1,25(OH)2D3 suggests that these genes, involved in the regulation of bone homeostasis, are additional mediators for 1,25(OH)2D3 signaling in osteoblasts.
Volume 173
Pages 185-193
Published 2017-10-1
DOI 10.1016/j.jsbmb.2017.02.005
PII S0960-0760(17)30039-0
PMID 28189595
PMC PMC9055571
MeSH Animals Calcitriol / metabolism* Cell Line Cell Proliferation Cells, Cultured Cytoskeletal Proteins Glycoproteins / genetics Membrane Proteins / genetics Mice Nerve Tissue Proteins / genetics Osteoblasts / cytology Osteoblasts / metabolism* Semaphorins / genetics* Transcriptional Activation*
IF 3.813
Human and Animal Cells MC3T3-E1(RCB1126)