Impact of targeted PPARγ disruption on bone remodeling

Peroxisome proliferator-activated receptor gamma (PPAR gamma), known as the master regulator of adipogenesis, has been regarded as a promising target for new anti-osteoporosis therapy due to its role in regulating bone marrow mesenchymal stem/progenitor cell (BMSC) lineage commitment. However, the precise mechanism underlying PPAR gamma regulation of bone is not clear as a bone-specific PPAR gamma conditional knockout (cKO) study has not been conducted and evidence showed that deletion of PPAR gamma in other tissues also have profound effect on bone. In this study, we show that mice deficiency of PPAR gamma in cells expressing a 3.6 kb type I collagen promoter fragment (PPAR(fl/fl):Col3.6-Cre) exhibits a moderate, site-dependent bone mass phenotype. In vitro studies showed that adipogenesis is abolished completely and osteoblastogenesis increased significantly in both primary bone marrow culture and the BMSCs isolated from PPAR gamma cKO mice. Histology and histomorphometry studies revealed significant increases in the numbers of osteoblasts and surface in the PPAR gamma cKO mice. Finally, we found that neither the differentiation nor the function of osteoclasts was affected in the PPAR gamma cKO mice. Together, our studies indicate that PPAR gamma plays an important role in bone remodeling by increasing the abundance of osteoblasts for repair, but not during skeletal development. (C) 2015 Elsevier Ireland Ltd. All rights reserved.