RRC ID |
62935
|
著者 |
Kito H, Morihiro H, Sakakibara Y, Endo K, Kajikuri J, Suzuki T, Ohya S.
|
タイトル |
Downregulation of the Ca2+-activated K+ channel KCa3.1 in mouse preosteoblast cells treated with vitamin D receptor agonist.
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ジャーナル |
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.
|
巻・号 |
319(2)
|
ページ |
C345-C358
|
公開日 |
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
|
リソース情報 |
ヒト・動物細胞 |
MC3T3-E1(RCB1126) |