PMID- 29029793
OWN - NLM
STAT- MEDLINE
DCOM- 20180529
LR  - 20191210
IS  - 1532-1991 (Electronic)
IS  - 0143-4160 (Linking)
VI  - 67
DP  - 2017 Nov
TI  - High extracellular Ca(2+) enhances the adipocyte accumulation of bone marrow 
      stromal cells through a decrease in cAMP.
PG  - 74-80
LID - S0143-4160(17)30107-0 [pii]
LID - 10.1016/j.ceca.2017.08.006 [doi]
AB  - Bone marrow stromal cells (BMSCs) are common progenitors of both adipocytes and 
      osteoblasts. We recently suggested that increased [Ca(2+)](o) caused by bone 
      resorption might accelerate adipocyte accumulation in response to treatment with 
      both insulin and dexamethasone. In this study, we investigated the mechanism by 
      which high [Ca(2+)](o) enhances adipocyte accumulation. We used primary mouse 
      BMSCs and evaluated the levels of adipocyte accumulation by measuring Oil Red O 
      staining. CaSR agonists (both Ca(2+) and Sr(2+)) enhanced the accumulation of 
      adipocytes among BMSCs in response to treatment with both insulin and 
      dexamethasone. We showed that high [Ca(2+)](o) decreases the concentration of 
      cAMP using ELISA. Real-time RT-PCR revealed that increasing the intracellular 
      concentration of cAMP (both chemical inducer (1muM forskolin and 200nM IBMX) and a 
      cAMP analog (10muM pCPT-cAMP)) suppressed the expression of PPARgamma and C/EBPalpha. In 
      addition, forskolin, IBMX, and pCPT-cAMP inhibited the enhancement in adipocyte 
      accumulation under high [Ca(2+)](o) in BMSCs. However, this inhibited effect was 
      not observed in BMSCs that were cultured in a basal concentration of [Ca(2+)](o). 
      We next observed that the accumulation of adipocytes in the of bone marrow of 
      middle-aged mice (25-40 weeks old) is higher than that of young mice (6 weeks 
      old) based on micro CT. ELISA results revealed that the concentration of cAMP in 
      the bone marrow mononuclear cells of middle-aged mice is lower than that of young 
      mice. These data suggest that increased [Ca(2+)](o) caused by bone resorption 
      might accelerate adipocyte accumulation through CaSR following a decrease in 
      cAMP.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Hashimoto, Ryota
AU  - Hashimoto R
AD  - Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, 
      Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: hryota@juntendo.ac.jp.
FAU - Katoh, Youichi
AU  - Katoh Y
AD  - Juntendo University Faculty of International Liberal Arts, Hongo 2-1-1, 
      Bunkyo-ku, Tokyo 112-8421, Japan; Department of Cardiology, Juntendo University 
      Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. 
      Electronic address: katoyo@juntendo.ac.jp.
FAU - Miyamoto, Yuki
AU  - Miyamoto Y
AD  - Juntendo University Faculty of Health Care and Nursing, Takasu 2-5-1, 
      Urayasu-shi, Chiba 279-0023, Japan.
FAU - Nakamura, Kyoko
AU  - Nakamura K
AD  - Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, 
      Bunkyo-ku, Tokyo 113-8421, Japan.
FAU - Itoh, Seigo
AU  - Itoh S
AD  - Department of Cardiology, Juntendo University Graduate School of Medicine, Hongo 
      2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
FAU - Daida, Hiroyuki
AU  - Daida H
AD  - Department of Cardiology, Juntendo University Graduate School of Medicine, Hongo 
      2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
FAU - Nakazato, Yuji
AU  - Nakazato Y
AD  - Center for Environmental Research, Department of Cardiology, Juntendo University 
      Faculty of Medicine Urayasu Hospital, Tomioka 2-1-1, Urayasu-shi, Chiba 279-0022, 
      Japan.
FAU - Okada, Takao
AU  - Okada T
AD  - Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, 
      Bunkyo-ku, Tokyo 113-8421, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170824
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (Azo Compounds)
RN  - 0 (CASR protein, mouse)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (CEBPA protein, mouse)
RN  - 0 (Insulin)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 1F7A44V6OU (Colforsin)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - G7S71FND9B (oil red O)
RN  - SY7Q814VUP (Calcium)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/pharmacology
MH  - Adipocytes/cytology/drug effects/*metabolism
MH  - Age Factors
MH  - Animals
MH  - Azo Compounds
MH  - Bone Marrow Cells/cytology/drug effects/metabolism
MH  - CCAAT-Enhancer-Binding Proteins/genetics/metabolism
MH  - Calcium/*metabolism
MH  - *Calcium Signaling
MH  - Cell Differentiation/drug effects
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/*metabolism
MH  - Dexamethasone/pharmacology
MH  - Gene Expression Regulation
MH  - Insulin/pharmacology
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/drug effects/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - PPAR gamma/genetics/metabolism
MH  - Primary Cell Culture
MH  - Receptors, Calcium-Sensing
MH  - Receptors, G-Protein-Coupled/*genetics/metabolism
MH  - Staining and Labeling/methods
OTO - NOTNLM
OT  - Adipogenesis
OT  - Bone marrow
OT  - Calcium
OT  - Cell proliferation
OT  - Mesenchymal stem cells (MSCs)
OT  - cAMP
EDAT- 2017/10/17 06:00
MHDA- 2018/05/31 06:00
CRDT- 2017/10/15 06:00
PHST- 2017/05/02 00:00 [received]
PHST- 2017/07/28 00:00 [revised]
PHST- 2017/08/19 00:00 [accepted]
PHST- 2017/10/15 06:00 [entrez]
PHST- 2017/10/17 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
AID - S0143-4160(17)30107-0 [pii]
AID - 10.1016/j.ceca.2017.08.006 [doi]
PST - ppublish
SO  - Cell Calcium. 2017 Nov;67:74-80. doi: 10.1016/j.ceca.2017.08.006. Epub 2017 Aug 
      24.