Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk

Iván Cárcamo-Orive, Ainhoa Gaztelumendi, Jesus Delgado-Calle, Naiara Tejados, Akaitz Dorronsoro, Jon Fernández-Rueda, Daniel J. Pennington, César Trigueros

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Although marrow adipocytes and osteoblasts derive from a common bone marrow stromal cells (BMSCs), the mechanisms that underlie osteoporosis-associated bone loss and marrow adipogenesis during prolonged steroid treatment are unclear. We show in human BMSCs (hBMSCs) that glucocorticoid receptor (GR) signaling in response to high concentrations of glucocorticoid (GC) supports adipogenesis but inhibits osteogenesis by reducing c-Jun expression and hBMSC proliferation. Conversely, significantly lower concentrations of GC, which permit hBMSC proliferation, are necessary for normal bone mineralization. In contrast, platelet-derived growth factor (PDGF) signaling increases both JNK/c-Jun activity and hBMSC expansion, favoring osteogenic differentiation instead of adipogenesis. Indeed, PDGF antagonizes the proadipogenic qualities of GC/GR signaling. Thus our results reveal a novel c-Jun-centered regulatory network of signaling pathways in differentiating hBMSCs that controls the proliferation-dependent balance between osteogenesis and adipogenesis.

Original languageEnglish (US)
Pages (from-to)2115-2125
Number of pages11
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume25
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Adipogenesis
Glucocorticoid Receptors
Transcription Factor AP-1
Mesenchymal Stromal Cells
Cell Differentiation
Cell Proliferation
Glucocorticoids
Platelet-Derived Growth Factor
Osteogenesis
Bone Marrow
Physiologic Calcification
Osteoblasts
Adipocytes
Human Activities
Osteoporosis
Steroids

Keywords

  • Adipose
  • Bone
  • Corticosteroid osteoporosis
  • Osteoblasts and stem cells

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk. / Cárcamo-Orive, Iván; Gaztelumendi, Ainhoa; Delgado-Calle, Jesus; Tejados, Naiara; Dorronsoro, Akaitz; Fernández-Rueda, Jon; Pennington, Daniel J.; Trigueros, César.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 25, No. 10, 10.2010, p. 2115-2125.

Research output: Contribution to journalArticle

Cárcamo-Orive, Iván ; Gaztelumendi, Ainhoa ; Delgado-Calle, Jesus ; Tejados, Naiara ; Dorronsoro, Akaitz ; Fernández-Rueda, Jon ; Pennington, Daniel J. ; Trigueros, César. / Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk. In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010 ; Vol. 25, No. 10. pp. 2115-2125.
@article{e67707334cec40fd8ff5ba0c910ac8be,
title = "Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk",
abstract = "Although marrow adipocytes and osteoblasts derive from a common bone marrow stromal cells (BMSCs), the mechanisms that underlie osteoporosis-associated bone loss and marrow adipogenesis during prolonged steroid treatment are unclear. We show in human BMSCs (hBMSCs) that glucocorticoid receptor (GR) signaling in response to high concentrations of glucocorticoid (GC) supports adipogenesis but inhibits osteogenesis by reducing c-Jun expression and hBMSC proliferation. Conversely, significantly lower concentrations of GC, which permit hBMSC proliferation, are necessary for normal bone mineralization. In contrast, platelet-derived growth factor (PDGF) signaling increases both JNK/c-Jun activity and hBMSC expansion, favoring osteogenic differentiation instead of adipogenesis. Indeed, PDGF antagonizes the proadipogenic qualities of GC/GR signaling. Thus our results reveal a novel c-Jun-centered regulatory network of signaling pathways in differentiating hBMSCs that controls the proliferation-dependent balance between osteogenesis and adipogenesis.",
keywords = "Adipose, Bone, Corticosteroid osteoporosis, Osteoblasts and stem cells",
author = "Iv{\'a}n C{\'a}rcamo-Orive and Ainhoa Gaztelumendi and Jesus Delgado-Calle and Naiara Tejados and Akaitz Dorronsoro and Jon Fern{\'a}ndez-Rueda and Pennington, {Daniel J.} and C{\'e}sar Trigueros",
year = "2010",
month = "10",
doi = "10.1002/jbmr.120",
language = "English (US)",
volume = "25",
pages = "2115--2125",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk

AU - Cárcamo-Orive, Iván

AU - Gaztelumendi, Ainhoa

AU - Delgado-Calle, Jesus

AU - Tejados, Naiara

AU - Dorronsoro, Akaitz

AU - Fernández-Rueda, Jon

AU - Pennington, Daniel J.

AU - Trigueros, César

PY - 2010/10

Y1 - 2010/10

N2 - Although marrow adipocytes and osteoblasts derive from a common bone marrow stromal cells (BMSCs), the mechanisms that underlie osteoporosis-associated bone loss and marrow adipogenesis during prolonged steroid treatment are unclear. We show in human BMSCs (hBMSCs) that glucocorticoid receptor (GR) signaling in response to high concentrations of glucocorticoid (GC) supports adipogenesis but inhibits osteogenesis by reducing c-Jun expression and hBMSC proliferation. Conversely, significantly lower concentrations of GC, which permit hBMSC proliferation, are necessary for normal bone mineralization. In contrast, platelet-derived growth factor (PDGF) signaling increases both JNK/c-Jun activity and hBMSC expansion, favoring osteogenic differentiation instead of adipogenesis. Indeed, PDGF antagonizes the proadipogenic qualities of GC/GR signaling. Thus our results reveal a novel c-Jun-centered regulatory network of signaling pathways in differentiating hBMSCs that controls the proliferation-dependent balance between osteogenesis and adipogenesis.

AB - Although marrow adipocytes and osteoblasts derive from a common bone marrow stromal cells (BMSCs), the mechanisms that underlie osteoporosis-associated bone loss and marrow adipogenesis during prolonged steroid treatment are unclear. We show in human BMSCs (hBMSCs) that glucocorticoid receptor (GR) signaling in response to high concentrations of glucocorticoid (GC) supports adipogenesis but inhibits osteogenesis by reducing c-Jun expression and hBMSC proliferation. Conversely, significantly lower concentrations of GC, which permit hBMSC proliferation, are necessary for normal bone mineralization. In contrast, platelet-derived growth factor (PDGF) signaling increases both JNK/c-Jun activity and hBMSC expansion, favoring osteogenic differentiation instead of adipogenesis. Indeed, PDGF antagonizes the proadipogenic qualities of GC/GR signaling. Thus our results reveal a novel c-Jun-centered regulatory network of signaling pathways in differentiating hBMSCs that controls the proliferation-dependent balance between osteogenesis and adipogenesis.

KW - Adipose

KW - Bone

KW - Corticosteroid osteoporosis

KW - Osteoblasts and stem cells

UR - http://www.scopus.com/inward/record.url?scp=77957676301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957676301&partnerID=8YFLogxK

U2 - 10.1002/jbmr.120

DO - 10.1002/jbmr.120

M3 - Article

C2 - 20499359

AN - SCOPUS:77957676301

VL - 25

SP - 2115

EP - 2125

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 10

ER -