Deletion of PPARγin Mesenchymal Lineage Cells Protects Against Aging-Induced Cortical Bone Loss in Mice

Jay Cao, Kehong Ding, Guodong Pan, Raysa Rosario, Yun Su, Yonggang Bao, Hongyan Zhou, Jianru Xu, Meghan E. McGee Lawrence, Mark W. Hamrick, Carlos M. Isales, Xingming Shi

Research output: Contribution to journalArticle

Abstract

Bone loss in aging is linked with chronic low-grade inflammation and the accumulation of marrowfat in animals and humans. Peroxisome proliferator-Activated receptor gamma (PPARγ), an adipogenic regulator, plays key roles in these biological processes. However, studies of the roles of PPARγin age-related bone loss and inflammation are lacking. We hypothesized that deletion of PPARγin bone marrow mesenchymal lineage cells would reduce bone loss with aging, potentially through a reduction in fat-generated inflammatory responses and an increase in osteoblastic activity. In the present study, we show that mice deficient of PPARγin Dermo1-expressing mesenchymal lineage cells (Dermo1-Cre:PPARγ?fl/fl) have reduced fat mass and increased cortical bone thickness but that deficiency of PPARγhad limited effect on protection of trabecular bone with aging as demonstrated by dual-energy X-ray absorptiometry, μCT, and histomorphometric analyses. Conditional knockout of PPARγreduced serum concentrations of adipokines, including adiponectin, resistin, and leptin, and reduced marrow stromal cell expression levels of inflammation-related genes. Inflammation genes involved in the interferon signaling pathway were reduced the most. These results demonstrate that disruption of the master adipogenic regulator, PPARγ, has a certain protective effect on aging-induced bone loss, suggesting that regulation of adipose function and modulation of interferon signaling are among the key mechanisms by which PPARγregulates bone homeostasis during aging process.

Original languageEnglish (US)
Pages (from-to)826-834
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume75
Issue number5
DOIs
StatePublished - Apr 17 2020

Keywords

  • Adipocyte
  • Aging
  • Bone loss
  • Inflammation
  • PPARγ

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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