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Bone morphogenic protein BMP7 induces adipocyte differentiation and uncoupling protein UCP1 expression in human bone marrow mesenchymal stem cells

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Abstract

In this work human bone marrow mesenchymal stem cells (hMSCs) have been differentiated into brown adipocytes by the bone morphogenic protein BMP7, and the morphological and biochemical changes of hMSCs occurring during the differentiation towards brown adipocytes have been investigated. After differentiation, the cells display the presence of numerous vacuoles full of lipids; staining with Oil Red reveals the typical multilocular organization of fat, and a compact network of actin microfilaments surrounding fat vacuoles appears. Uncoupling protein 1 (UCP1), a mitochondrial protein characteristic of the brown adipose tissue, only visible by Western blotting in hMSCs, exhibits a marked increase after the second cycle of adipogenic induction and even more after the fourth cycle, while the mitochondria change their localization from scattered throughout the cytoplasm to mainly near the fat vacuoles. In differentiated brown adipocytes mitochondria close to the vacuoles display a low membrane potential most likely due to the abundant presence of UCP1. Hopefully the additional knowledge about the role of UCP1 in hMSCs and brown adipocytes will be useful in developing strategies for the treatment of several diseases, such as obesity and type 2 diabetes.

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Abbreviations

ANOVA:

Analysis of variance

β-AR:

β-adrenergic receptors

BAT:

Brown adipose tissue

BMP:

Bone morphogenic protein

BSA:

Bovine serum albumin

CLSM:

Confocal laser scanning microscope

DAPI:

4′,6-Diamidino-2-phenylindole

EDTA:

Ethylenediaminetetraacetic acid

EMS:

Electron microscopy sciences

FBS:

Fetal bovine serum

FESEM:

Field emission scanning electron microscope

FITC:

Fluorescein isothiocyanate

hMSCs:

Human mesenchymal stem cells

MEM:

Minimum essential medium

MSCs:

Mesenchymal stromal cells

PBS:

Phosphate buffered saline

S.E.M.:

Standard error of mean

SDS-PAGE:

Sodium dodecyl sulphate-polyAcrylamide gel electrophoresis

SEM:

Scanning electron microscope

TGF-β:

Transforming growth factor β

UCP1:

Uncoupling protein 1

WAT:

White adipocyte tissue

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Authors and Affiliations

  1. Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123, Catania, Italy

    Maria Teresa Cambria, Giusy Villaggio & Fulvia Sinatra

  2. Department of Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95125, Catania, Italy

    Concetta Federico & Salvatore Saccone

Authors
  1. Maria Teresa Cambria
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  2. Giusy Villaggio
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  3. Concetta Federico
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  4. Salvatore Saccone
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  5. Fulvia Sinatra
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Correspondence to Maria Teresa Cambria.

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Cambria, M.T., Villaggio, G., Federico, C. et al. Bone morphogenic protein BMP7 induces adipocyte differentiation and uncoupling protein UCP1 expression in human bone marrow mesenchymal stem cells. Rend. Fis. Acc. Lincei 28, 635–641 (2017). https://doi.org/10.1007/s12210-017-0643-x

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