Evidence for multiple peroxisome proliferator-activated receptor γ transcripts in bone: Fine-tuning by hormonal regulation and mRNA stability

Abstract 

The expression, regulation and functional significance of multiple peroxisome proliferator-activated receptor γ transcript variants in bone were studied. PPARG transcripts giving rise to PPARg-1 protein were expressed in human osteoblasts, whereas PPARG-2 transcript and protein remained virtually absent. PPARG expression underwent homologous regulation, was upregulated during differentiation and directly induced by the osteogenic hormone dexamethasone, suggesting a role for PPARg-1 in osteogenesis. Differences between the stabilities of PPARG-1, -3 and -4 were observed. We hypothesize that cell-specific expression patterns of multiple PPARG transcript variants encoding for the same protein but differing in mRNA stabilities enable a fine-tuning of PPARG action, which eventually supports a well-adjusted signal transduction between the cell and its environment.

Abbreviations: PPARG, peroxisome proliferator-activated receptor γ, DEX, dexamethasone, ROSI, rosiglitazone, VSMC, vascular smooth muscle cells, MSC, mesenchymal stem cells

Keywords: Peroxisome proliferator-activated receptor γ, Osteoblast, Glucocorticoids, Rosiglitazone, mRNA Stability, Alternative splicing