GH prevents adipogenic differentiation of mesenchymal stromal stem cells derived from human trabecular bone via canonical Wnt signaling

S Bolamperti, M Signo, A Spinello, GL Moro, G Fraschini, F Guidobono, A Rubinacci, I Villa

Research output: Contribution to journalArticle

Abstract

The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. © 2018 Elsevier Inc.
Original languageEnglish
Pages (from-to)136-144
Number of pages9
JournalBone
Volume112
Issue number5
DOIs
Publication statusPublished - 2018

Fingerprint

Mesenchymal Stromal Cells
CCAAT-Enhancer-Binding Protein-alpha
Osteoprotegerin
Catenins
Lipogenesis
Lipoprotein Lipase
Adiponectin
Gene Expression
Bone Marrow
Frizzled Receptors
Adipogenesis
Bone Diseases
Enzymes
Adipocytes
Osteogenesis
Osteoporosis
Cell Differentiation
Fats
Lipids
Cancellous Bone

Cite this

GH prevents adipogenic differentiation of mesenchymal stromal stem cells derived from human trabecular bone via canonical Wnt signaling. / Bolamperti, S; Signo, M; Spinello, A; Moro, GL; Fraschini, G; Guidobono, F; Rubinacci, A; Villa, I.

In: Bone, Vol. 112, No. 5, 2018, p. 136-144.

Research output: Contribution to journalArticle

@article{b5fdfe5c284845d9a8b07b39695f1107,
title = "GH prevents adipogenic differentiation of mesenchymal stromal stem cells derived from human trabecular bone via canonical Wnt signaling",
abstract = "The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. {\circledC} 2018 Elsevier Inc.",
author = "S Bolamperti and M Signo and A Spinello and GL Moro and G Fraschini and F Guidobono and A Rubinacci and I Villa",
year = "2018",
doi = "10.1016/j.bone.2018.04.014",
language = "English",
volume = "112",
pages = "136--144",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - GH prevents adipogenic differentiation of mesenchymal stromal stem cells derived from human trabecular bone via canonical Wnt signaling

AU - Bolamperti, S

AU - Signo, M

AU - Spinello, A

AU - Moro, GL

AU - Fraschini, G

AU - Guidobono, F

AU - Rubinacci, A

AU - Villa, I

PY - 2018

Y1 - 2018

N2 - The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. © 2018 Elsevier Inc.

AB - The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of β-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of β-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBPα and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG. The present study supports the hypothesis that when GH secretion declines as in aging, the fat in the bone-marrow cavities increases and the osteogenic capacity of the MSC pool is reduced due to a decrease in Wnt signaling. © 2018 Elsevier Inc.

U2 - 10.1016/j.bone.2018.04.014

DO - 10.1016/j.bone.2018.04.014

M3 - Article

VL - 112

SP - 136

EP - 144

JO - Bone

JF - Bone

SN - 8756-3282

IS - 5

ER -