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Regulation of oligodendrocyte progenitor cell maturation by PPARδ: effects on bone morphogenetic proteins.

Vittoria Simonini M, Polak PE, Boullerne AI, Peters JM, Richardson JC, Feinstein DL - ASN Neuro (2010)

Bottom Line: In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells), and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins).This was due to activation of PPARδ since process formation was reduced in PPARδ- compared with wild-type OPCs.In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, University of Illinois, Chicago, IL 60612, U.S.A.

ABSTRACT
In EAE (experimental autoimmune encephalomyelitis), agonists of PPARs (peroxisome proliferator-activated receptors) provide clinical benefit and reduce damage. In contrast with PPARγ, agonists of PPARδ are more effective when given at later stages of EAE and increase myelin gene expression, suggesting effects on OL (oligodendrocyte) maturation. In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells), and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins). We show that effects of GW0742 are mediated through PPARδ since no amelioration of EAE clinical scores was observed in PPARδ- mice. In OPCs derived from E13 mice (where E is embryonic day), GW0742, but not the PPARγ agonist pioglitazone, increased the number of myelin-producing OLs. This was due to activation of PPARδ since process formation was reduced in PPARδ- compared with wild-type OPCs. In both OPCs and enriched astrocyte cultures, GW0742 increased noggin protein expression; however, noggin mRNA was only increased in astrocytes. In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPARδ plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists.

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GW0742 increases noggin expression in OPC culturesMouse E13 OPCs were grown for 5 days in differentiation medium, then treated with (A) vehicle or (B) 3 μM GW0742 for 24 h. Cells were then fixed and immunostained for noggin. Cell counting was carried out to quantify the total number of spheres and total number of spheres stained for noggin in seven fields of view for each condition taken at 20×magnification. There was a similar number of spheres in the two groups (20.4±3 compared with 28.0±5, average number of spheres per field, DMSO compared with GW0742, P>0.05). GW0742 significantly increased the number of noggin-stained spheres (from 7.4±2 to 21.4±4 per field, P<0.01) and the percentage of noggin-stained spheres increased from 40±10% to 79±6% (P<0.01). Representative images are shown for each condition.
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Figure 6: GW0742 increases noggin expression in OPC culturesMouse E13 OPCs were grown for 5 days in differentiation medium, then treated with (A) vehicle or (B) 3 μM GW0742 for 24 h. Cells were then fixed and immunostained for noggin. Cell counting was carried out to quantify the total number of spheres and total number of spheres stained for noggin in seven fields of view for each condition taken at 20×magnification. There was a similar number of spheres in the two groups (20.4±3 compared with 28.0±5, average number of spheres per field, DMSO compared with GW0742, P>0.05). GW0742 significantly increased the number of noggin-stained spheres (from 7.4±2 to 21.4±4 per field, P<0.01) and the percentage of noggin-stained spheres increased from 40±10% to 79±6% (P<0.01). Representative images are shown for each condition.

Mentions: Quantification of the cell numbers in Figure 2 was performed manually, and in Figures 4 and 6 performed using Zeiss Axiovision version 4.5. Comparisons between groups were made using a Student's unpaired t test. Comparisons of the number of stained cells in Figure 2 was done using χ2 analysis. Comparison of clinical signs in WT (wild-type) compared with PPARδ- mice was performed by two-way repeated measures ANOVA using data from day 25 (the start of treatment) to the end of the study (day 49). Values are means±S.E.M., and for all comparisons significance was taken at P<0.05.


Regulation of oligodendrocyte progenitor cell maturation by PPARδ: effects on bone morphogenetic proteins.

Vittoria Simonini M, Polak PE, Boullerne AI, Peters JM, Richardson JC, Feinstein DL - ASN Neuro (2010)

GW0742 increases noggin expression in OPC culturesMouse E13 OPCs were grown for 5 days in differentiation medium, then treated with (A) vehicle or (B) 3 μM GW0742 for 24 h. Cells were then fixed and immunostained for noggin. Cell counting was carried out to quantify the total number of spheres and total number of spheres stained for noggin in seven fields of view for each condition taken at 20×magnification. There was a similar number of spheres in the two groups (20.4±3 compared with 28.0±5, average number of spheres per field, DMSO compared with GW0742, P>0.05). GW0742 significantly increased the number of noggin-stained spheres (from 7.4±2 to 21.4±4 per field, P<0.01) and the percentage of noggin-stained spheres increased from 40±10% to 79±6% (P<0.01). Representative images are shown for each condition.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2807733&req=5

Figure 6: GW0742 increases noggin expression in OPC culturesMouse E13 OPCs were grown for 5 days in differentiation medium, then treated with (A) vehicle or (B) 3 μM GW0742 for 24 h. Cells were then fixed and immunostained for noggin. Cell counting was carried out to quantify the total number of spheres and total number of spheres stained for noggin in seven fields of view for each condition taken at 20×magnification. There was a similar number of spheres in the two groups (20.4±3 compared with 28.0±5, average number of spheres per field, DMSO compared with GW0742, P>0.05). GW0742 significantly increased the number of noggin-stained spheres (from 7.4±2 to 21.4±4 per field, P<0.01) and the percentage of noggin-stained spheres increased from 40±10% to 79±6% (P<0.01). Representative images are shown for each condition.
Mentions: Quantification of the cell numbers in Figure 2 was performed manually, and in Figures 4 and 6 performed using Zeiss Axiovision version 4.5. Comparisons between groups were made using a Student's unpaired t test. Comparisons of the number of stained cells in Figure 2 was done using χ2 analysis. Comparison of clinical signs in WT (wild-type) compared with PPARδ- mice was performed by two-way repeated measures ANOVA using data from day 25 (the start of treatment) to the end of the study (day 49). Values are means±S.E.M., and for all comparisons significance was taken at P<0.05.

Bottom Line: In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells), and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins).This was due to activation of PPARδ since process formation was reduced in PPARδ- compared with wild-type OPCs.In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, University of Illinois, Chicago, IL 60612, U.S.A.

ABSTRACT
In EAE (experimental autoimmune encephalomyelitis), agonists of PPARs (peroxisome proliferator-activated receptors) provide clinical benefit and reduce damage. In contrast with PPARγ, agonists of PPARδ are more effective when given at later stages of EAE and increase myelin gene expression, suggesting effects on OL (oligodendrocyte) maturation. In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells), and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins). We show that effects of GW0742 are mediated through PPARδ since no amelioration of EAE clinical scores was observed in PPARδ- mice. In OPCs derived from E13 mice (where E is embryonic day), GW0742, but not the PPARγ agonist pioglitazone, increased the number of myelin-producing OLs. This was due to activation of PPARδ since process formation was reduced in PPARδ- compared with wild-type OPCs. In both OPCs and enriched astrocyte cultures, GW0742 increased noggin protein expression; however, noggin mRNA was only increased in astrocytes. In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPARδ plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists.

Show MeSH
Related in: MedlinePlus