Impact of targeted PPARγ disruption on bone remodeling

Jay Cao, Guomin Ou, Nianlan Yang, Kehong Ding, Barbara E. Kream, Mark W. Hamrick, Carlos M. Isales, Xing Ming Shi

Research output: Contribution to journalReview article

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume410
DOIs
StatePublished - Jul 5 2015

Keywords

  • Aging
  • Bone loss
  • MSC
  • Osteoblasts
  • PPARγ

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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