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The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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High extracellular Ca2+ enhances the adipocyte accumulation of bone marrow stromal cells through a decrease in cAMP.

Ryota Hashimoto1, Youichi Katoh2, Yuki Miyamoto3

  • 1Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.

Cell Calcium
|October 15, 2017
PubMed
Summary
This summary is machine-generated.

High extracellular calcium (Ca2+) levels, often seen with bone resorption, accelerate bone marrow stromal cell (BMSC) differentiation into fat cells. This process involves decreased cAMP signaling, suggesting a new mechanism for age-related bone marrow changes.

Keywords:
AdipogenesisBone marrowCalciumCell proliferationMesenchymal stem cells (MSCs)cAMP

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Bone Biology

Background:

  • Bone marrow stromal cells (BMSCs) differentiate into both adipocytes and osteoblasts.
  • Increased extracellular calcium ([Ca2+]o) due to bone resorption may promote adipocyte accumulation, particularly with insulin and dexamethasone treatment.

Purpose of the Study:

  • To investigate the mechanism by which elevated extracellular calcium ([Ca2+]o) enhances adipocyte accumulation in BMSCs.
  • To explore the role of cAMP signaling in this calcium-mediated process.

Main Methods:

  • Primary mouse BMSCs were used to assess adipocyte accumulation via Oil Red O staining.
  • Calcium-sensing receptor (CaSR) agonists (Ca2+, Sr2+) were applied.
  • cAMP levels were measured using ELISA.
  • Gene expression of adipogenic factors (PPARγ, C/EBPα) was analyzed by real-time RT-PCR.
  • Micro CT was used to compare adipocyte accumulation in young versus middle-aged mice.

Main Results:

  • CaSR agonists enhanced adipocyte accumulation in BMSCs treated with insulin and dexamethasone.
  • High [Ca2+]o decreased intracellular cAMP concentrations.
  • Increasing intracellular cAMP suppressed adipogenic gene expression and inhibited high [Ca2+]o-induced adipocyte accumulation.
  • Middle-aged mice showed higher bone marrow adiposity and lower cAMP levels compared to young mice.

Conclusions:

  • Elevated extracellular calcium ([Ca2+]o) accelerates adipocyte accumulation in BMSCs, potentially through CaSR activation and subsequent cAMP reduction.
  • This mechanism may contribute to the increased adiposity observed in the bone marrow of aging individuals.