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Impact of targeted PPARγ disruption on bone remodeling

Author:
Jay Cao, Guomin Ou, Nianlan Yang, Kehong Ding, Barbara E. Kream, Mark W. Hamrick, Carlos M. Isales, Xing-Ming Shi
Source:
Molecular and cellular endocrinology 2015 v.410 pp. 27-34
ISSN:
0303-7207
Subject:
adipogenesis, bone density, bone marrow, collagen, histology, in vitro studies, knockout mutants, mice, osteoblasts, osteoclasts, phenotype, promoter regions, skeletal development, stem cells, transcription factors
Abstract:
Peroxisome proliferator-activated receptor gamma (PPARγ), 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 PPARγ regulation of bone is not clear as a bone-specific PPARγ conditional knockout (cKO) study has not been conducted and evidence showed that deletion of PPARγ in other tissues also have profound effect on bone. In this study, we show that mice deficiency of PPARγ in cells expressing a 3.6 kb type I collagen promoter fragment (PPARfl/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 PPARγ cKO mice. Histology and histomorphometry studies revealed significant increases in the numbers of osteoblasts and surface in the PPARγ cKO mice. Finally, we found that neither the differentiation nor the function of osteoclasts was affected in the PPARγ cKO mice. Together, our studies indicate that PPARγ plays an important role in bone remodeling by increasing the abundance of osteoblasts for repair, but not during skeletal development.
Agid:
61178
Handle:
10113/61178