Deletion of PPARγ in mesenchymal lineage cells protects against aging-induced cortical bone loss in mice

J Cao, K Ding, G Pan, R Rosario, Y Su… - The Journals of …, 2020 - academic.oup.com
J Cao, K Ding, G Pan, R Rosario, Y Su, Y Bao, H Zhou, J Xu, ME McGee Lawrence
The Journals of Gerontology: Series A, 2020academic.oup.com
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 PPARγ in age-related bone loss and inflammation are lacking. We
hypothesized that deletion of PPARγ in bone marrow mesenchymal lineage cells would
reduce bone loss with aging, potentially through a reduction in fat-generated inflammatory …
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 PPARγ in age-related bone loss and inflammation are lacking. We hypothesized that deletion of PPARγ in 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 PPARγ in Dermo1-expressing mesenchymal lineage cells (Dermo1-Cre:PPARγ fl/fl) have reduced fat mass and increased cortical bone thickness but that deficiency of PPARγ had limited effect on protection of trabecular bone with aging as demonstrated by dual-energy X-ray absorptiometry, µCT, and histomorphometric analyses. Conditional knockout of PPARγ reduced 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 PPARγ regulates bone homeostasis during aging process.
Oxford University Press