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

20 Citations (Scopus)

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

Fingerprint

Bone Remodeling
PPAR gamma
Bone
Knockout Mice
Bone and Bones
Adipogenesis
Osteoblasts
Mesenchymal Stromal Cells
Bone Marrow
Histology
Cell Lineage
Osteoclasts
Collagen Type I
Stem cells
Osteoporosis
Repair
Cells
Tissue

Keywords

  • Aging
  • Bone loss
  • MSC
  • Osteoblasts
  • PPARγ

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Impact of targeted PPARγ disruption on bone remodeling. / Cao, Jay; Ou, Guomin; Yang, Nianlan; Ding, Kehong; Kream, Barbara E.; Hamrick, Mark W; Isales, Carlos M; Shi, Xing Ming.

In: Molecular and Cellular Endocrinology, Vol. 410, 05.07.2015, p. 27-34.

Research output: Contribution to journalReview article

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AU - Ou, Guomin

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AU - Hamrick, Mark W

AU - Isales, Carlos M

AU - Shi, Xing Ming

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