Expression of PPARγ and β/δ in Human Primary Osteoblastic Cells: Influence of Polyunsaturated Fatty Acids

As previously reported, the age-related association between bone loss and increased marrow adipose volume may involve inhibitory effects of polyunsaturated fatty acids (PUFAs) potentially released by medullary adipocytes on osteoblastic proliferation and cell cycle progression. Because PUFAs have been reported to activate peroxisome proliferator-activated receptors (PPARs), we investigated the expression of these nuclear receptors in human primary osteoblastic (hOB) cells and examined the effects of natural PPAR ligands on hOB cell proliferation. We demonstrated basic expressions of PPARγ and PPARβ/δ in hOB cells at the protein level. As already shown for PUFAs, a short-term treatment with 15deoxy-Δ^12,14 –prostaglandin J2 (15dPGJ2) or prostacyclin (PGI2), which are specific ligands for PPARγ and PPARβ/δ, respectively, also significantly inhibited hOB cell proliferation. Given that the cell cycle withdrawal resulting from PPARγ activation was often associated with the induction of cell differentiation, long-term effects of PUFAs and 15dPGJ2 were also assessed on the expression levels of transcription factors. PUFAs and 15dPGJ2 enhanced the expression of PPARγ in hOB cells. It is of interest to note that PPARγ protein level was dose-dependently increased, whereas that of Cbfal was decreased by a fatty acid–rich serum. In conclusion, this study shows that PPARγ and β/δ are expressed by hOB cells. The results further suggest that the short-term antiproliferative effect of PUFAs may involve PPAR activation in hOB cells, resulting in a cell cycle withdrawal favorable for the long-term differentiating effects of fatty acids. Further studies are now required to confirm the functional role of PPARs in the antiproliferative effects of PUFAs in hOB cells.