Transforming growth factor-{beta} inhibits CCAAT/enhancer-binding protein expression and PPAR{gamma} activity in unloaded bone marrow stromal cells

Journal Article · Tue Feb 01 04:00:00 EST 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2004.09.013· OSTI ID:20717528

Ahdjoudj, S ^[1]; Kaabeche, K ^[1]; Holy, X ^[2]; Fromigue, O ^[1]; Modrowski, D ^[1]; Zerath, E ^[2]; Marie, P J ^[1]

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1. Unit 606 INSERM, Laboratory of Osteoblast Biology and Pathology, Paris (France)
2. IMASSA-CERMA, Dept of Aerospace Physiology, Bretigny sur Orge (France)

The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-{beta}2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP){alpha} and C/EBP{beta} {alpha} at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}2) transcripts at 7 days. TGF-{beta}2 administration in unloaded rats corrected the rise in C/EBP{alpha} and C/EBP{beta} transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPAR{gamma}2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBP{alpha} and C/EBP{beta} expression by TGF-{beta}2 was associated with increased PPAR{gamma} serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPAR{gamma} transactivating activity. The sequential inhibitory effect of TGF-{beta}2 on C/EBP{alpha}, C/EBP{beta}, and PPAR{gamma}2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-{beta}2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBP{alpha}, C/EBP{beta}, and PPAR{gamma} expression and activity, which provides a sequential mechanism by which TGF-{beta}2 regulates adipogenic differentiation of bone marrow stromal cells in vivo.

• OSTI ID: 20717528
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 303; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BONE MARROW
GROWTH FACTORS
IN VIVO
INHIBITION
LIMBS
PHOSPHORYLATION
POLYMERASE CHAIN REACTION
RATS
RECEPTORS
SERINE
SKELETON
TRANSCRIPTION
TRANSCRIPTION FACTORS