RRC ID 62935
Author Kito H, Morihiro H, Sakakibara Y, Endo K, Kajikuri J, Suzuki T, Ohya S.
Title Downregulation of the Ca2+-activated K+ channel KCa3.1 in mouse preosteoblast cells treated with vitamin D receptor agonist.
Journal Am J Physiol Cell Physiol
Abstract The maturity of osteoblasts by proliferation and differentiation in preosteoblasts is essential for maintaining bone homeostasis. The beneficial effects of vitamin D on bone homeostasis in mammals have been demonstrated experimentally and clinically. However, the direct actions of vitamin D on preosteoblasts remain to be fully elucidated. In this study, we found that the functional activity of intermediate-conductance Ca2+-activated K+ channels (KCa3.1) positively regulated cell proliferation in MC3T3-E1 cells derived from mouse preosteoblasts by enhancing intracellular Ca2+ signaling. We examined the effects of treatment with vitamin D receptor (VDR) agonist on the expression and activity of KCa3.1 by real-time PCR examination, Western blotting, Ca2+ imaging, and patch clamp analyses in mouse MC3T3-E1 cells. Following the downregulation of KCa3.1 transcriptional modulators such as Fra-1 and HDAC2, KCa3.1 activity was suppressed in MC3T3-E1 cells treated with VDR agonists. Furthermore, application of the KCa3.1 activator DCEBIO attenuated the VDR agonist-evoked suppression of cell proliferation rate. These findings suggest that a decrease in KCa3.1 activity is involved in the suppression of cell proliferation rate in VDR agonist-treated preosteoblasts. Therefore, KCa3.1 plays an important role in bone formation by promoting osteoblastic proliferation under physiological conditions.
Volume 319(2)
Pages C345-C358
Published 2020-8-1
DOI 10.1152/ajpcell.00587.2019
PMID 32520608
MeSH 3T3 Cells Animals Benzimidazoles / pharmacology Calcium / metabolism Calcium Signaling / genetics Cell Differentiation / drug effects Cell Proliferation / drug effects Gene Expression Regulation / genetics Histone Deacetylase 2 / genetics Humans Intermediate-Conductance Calcium-Activated Potassium Channels / genetics* Mice Osteoblasts / cytology Osteoblasts / metabolism* Osteogenesis / drug effects Osteogenesis / genetics Patch-Clamp Techniques Proto-Oncogene Proteins c-fos / genetics Receptors, Calcitriol / agonists Receptors, Calcitriol / genetics* Signal Transduction / drug effects Vitamin D / genetics*
IF 3.485
Human and Animal Cells MC3T3-E1(RCB1126)