Fol. Biol. 2011, 57, 133-138
Effect of PPAR-γ Agonist Rosiglitazone on Bone Mineral Density and Serum Adipokines in C57BL/6 Male Mice
Thiazolinediones (TZD) are widely used to treat type 2 diabetes, but their mechanism of action still remains only partially understood. Although the in vitro effects of TZD on osteoblastogenesis are well recognized, the in vivo consequences of these compounds on bone turnover are less understood and rather controversial. We demonstrate that a 9-week oral treatment with rosiglitazone in C57BL/6 male mice resulted in significant bone loss that was not dose dependent. The bones of the rosiglitazone-treated mice were characterized by reduction of bone density, and ash, calcium and phosphorus content. Rosiglitazone-treated mice had significantly thinner cortical widths. In contrast to serum TrACP expressed by action of osteoclasts, serum B-ALP activity, which serves as a marker of osteoblastic activity, was significantly lower in the rosiglitazone-fed animals. We did not find any differences in circulating levels of adipokines that could eventually explain rosiglitazone action. As the decrease in osteoblastic activity was demonstrated after rosiglitazone treatment, we anticipated changes in the haematopoietic stem cell pool. These cells seed in endosteal niches which comprise osteoblasts in order to maintain their stem cell function. In our study we did not see any significant influence of rosiglitazone administration on stem cells or any impairment in the lineage restrictions of rosiglitazone-treated stem cells. Our data demonstrate that rosiglitazone administration causes a loss of bone mass in cortical bone, possibly through a decrease in bone formation expressed by decreased B-ALP in male C57BL/6 mice. The levels of adipokines do not play any role.
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Funding
This work was supported by the research projects MSM 0021620806, MZOVFN2005 and LC06044 granted by the Ministry of Education, Youth and Sports of the Czech Republic.
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Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
