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Signaling Crosstalk between PPARγ and BMP2 in Mesenchymal Stem Cells.

Takada I, Yogiashi Y, Kato S - PPAR Res (2012)

Bottom Line: Among these factors, BMP2 strongly induces bone formation, but the effect of BMP2 on PPARγ function remains unclear.We examined the effect of BMP2 and PPARγ in ST2 cells and found that PPARγ activation affected BMP2's signaling pathway through epigenetic regulation.These results suggest that the order of treatment with BMP2 and a PPARγ ligand is critical for adipogenesis and osteoblastogenesis switching in MSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Tissue Biology, School of Medicine, Keio University, Tokyo 160-8582, Japan ; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo 160-8582, Japan.

ABSTRACT
Recent studies have revealed that PPARγ's transactivation function is regulated by extracellular signals. In particular, cytokines and Wnt family proteins suppress the ligand-inducible transactivation function of PPARγ and attenuate adipogenesis/osteoblastogenesis switching in mesenchymal stem cells (MSCs). For example, Wnt5a suppresses PPARγ transcriptional activity through the NLK/SETDB1/CHD7 pathway. Among these factors, BMP2 strongly induces bone formation, but the effect of BMP2 on PPARγ function remains unclear. We examined the effect of BMP2 and PPARγ in ST2 cells and found that PPARγ activation affected BMP2's signaling pathway through epigenetic regulation. Although BMP2 did not interfere with PPARγ-mediated adipogenesis, BMP2 increased mRNA expression levels of PPARγ target genes (such as Fabp4 and Nr1h3) when cells were first treated with troglitazone (TRO). Moreover, PPARγ activation affected BMP2 through enhancement of histone activation markers (acetylated histone H3 and trimethylated Lys4 of histone H3) on the Runx2 promoter. After TRO treatment for three hours, BMP2 enhanced the levels of active histone marks on the promoter of a PPARγ target gene. These results suggest that the order of treatment with BMP2 and a PPARγ ligand is critical for adipogenesis and osteoblastogenesis switching in MSCs.

No MeSH data available.


The effect of BMP2 and TRO on adipocyte and osteoblast differentiation of ST2 cells. The scheme of experiments are shown in upper panel. ST2 cells were cultured with one μM troglitazone (TRO) or 50 ng/mL human recombinant BMP2 for seven days. The cells were fixed with 4% formaldehyde/PBS for five min at room temperature, and stained with Oil red O or for alkaline phosphatase (ALPL) activity. Scale bar means 50 μm.
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fig1: The effect of BMP2 and TRO on adipocyte and osteoblast differentiation of ST2 cells. The scheme of experiments are shown in upper panel. ST2 cells were cultured with one μM troglitazone (TRO) or 50 ng/mL human recombinant BMP2 for seven days. The cells were fixed with 4% formaldehyde/PBS for five min at room temperature, and stained with Oil red O or for alkaline phosphatase (ALPL) activity. Scale bar means 50 μm.

Mentions: To elucidate the molecular link between BMP2 and PPARγ, we first examined the effect of BMP2 on adipocyte/osteoblast differentiation by analyzing the response of ST2 cells. These cells are derived from mouse bone marrow stromal cells and can differentiate into adipocytes or osteoblasts [25]. We treated ST2 cells with one μM troglitazone (TRO) as a PPARγ ligand and/or 50 ng/mL BMP2 to induce adipocytes or osteoblasts. We confirmed adipocyte differentiation by Oil red O staining and osteoblasts by staining for alkaline phosphatase (ALPL) activity. As previously reported, TRO induced adipogenesis but not osteoblastogenesis. However, ST2 cells treated with both TRO and BMP2 for seven days underwent adipogenesis and osteoblastogenesis (Figure 1). These results show that PPARγ and BMP2 do not interfere with one another.


Signaling Crosstalk between PPARγ and BMP2 in Mesenchymal Stem Cells.

Takada I, Yogiashi Y, Kato S - PPAR Res (2012)

The effect of BMP2 and TRO on adipocyte and osteoblast differentiation of ST2 cells. The scheme of experiments are shown in upper panel. ST2 cells were cultured with one μM troglitazone (TRO) or 50 ng/mL human recombinant BMP2 for seven days. The cells were fixed with 4% formaldehyde/PBS for five min at room temperature, and stained with Oil red O or for alkaline phosphatase (ALPL) activity. Scale bar means 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539391&req=5

fig1: The effect of BMP2 and TRO on adipocyte and osteoblast differentiation of ST2 cells. The scheme of experiments are shown in upper panel. ST2 cells were cultured with one μM troglitazone (TRO) or 50 ng/mL human recombinant BMP2 for seven days. The cells were fixed with 4% formaldehyde/PBS for five min at room temperature, and stained with Oil red O or for alkaline phosphatase (ALPL) activity. Scale bar means 50 μm.
Mentions: To elucidate the molecular link between BMP2 and PPARγ, we first examined the effect of BMP2 on adipocyte/osteoblast differentiation by analyzing the response of ST2 cells. These cells are derived from mouse bone marrow stromal cells and can differentiate into adipocytes or osteoblasts [25]. We treated ST2 cells with one μM troglitazone (TRO) as a PPARγ ligand and/or 50 ng/mL BMP2 to induce adipocytes or osteoblasts. We confirmed adipocyte differentiation by Oil red O staining and osteoblasts by staining for alkaline phosphatase (ALPL) activity. As previously reported, TRO induced adipogenesis but not osteoblastogenesis. However, ST2 cells treated with both TRO and BMP2 for seven days underwent adipogenesis and osteoblastogenesis (Figure 1). These results show that PPARγ and BMP2 do not interfere with one another.

Bottom Line: Among these factors, BMP2 strongly induces bone formation, but the effect of BMP2 on PPARγ function remains unclear.We examined the effect of BMP2 and PPARγ in ST2 cells and found that PPARγ activation affected BMP2's signaling pathway through epigenetic regulation.These results suggest that the order of treatment with BMP2 and a PPARγ ligand is critical for adipogenesis and osteoblastogenesis switching in MSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Tissue Biology, School of Medicine, Keio University, Tokyo 160-8582, Japan ; Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo 160-8582, Japan.

ABSTRACT
Recent studies have revealed that PPARγ's transactivation function is regulated by extracellular signals. In particular, cytokines and Wnt family proteins suppress the ligand-inducible transactivation function of PPARγ and attenuate adipogenesis/osteoblastogenesis switching in mesenchymal stem cells (MSCs). For example, Wnt5a suppresses PPARγ transcriptional activity through the NLK/SETDB1/CHD7 pathway. Among these factors, BMP2 strongly induces bone formation, but the effect of BMP2 on PPARγ function remains unclear. We examined the effect of BMP2 and PPARγ in ST2 cells and found that PPARγ activation affected BMP2's signaling pathway through epigenetic regulation. Although BMP2 did not interfere with PPARγ-mediated adipogenesis, BMP2 increased mRNA expression levels of PPARγ target genes (such as Fabp4 and Nr1h3) when cells were first treated with troglitazone (TRO). Moreover, PPARγ activation affected BMP2 through enhancement of histone activation markers (acetylated histone H3 and trimethylated Lys4 of histone H3) on the Runx2 promoter. After TRO treatment for three hours, BMP2 enhanced the levels of active histone marks on the promoter of a PPARγ target gene. These results suggest that the order of treatment with BMP2 and a PPARγ ligand is critical for adipogenesis and osteoblastogenesis switching in MSCs.

No MeSH data available.