TY - JOUR
T1 - Deletion of PPARγin Mesenchymal Lineage Cells Protects Against Aging-Induced Cortical Bone Loss in Mice
AU - Cao, Jay
AU - Ding, Kehong
AU - Pan, Guodong
AU - Rosario, Raysa
AU - Su, Yun
AU - Bao, Yonggang
AU - Zhou, Hongyan
AU - Xu, Jianru
AU - McGee Lawrence, Meghan E.
AU - Hamrick, Mark W.
AU - Isales, Carlos M.
AU - Shi, Xingming
N1 - Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2020/4/17
Y1 - 2020/4/17
N2 - 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.
AB - 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.
KW - Adipocyte
KW - Aging
KW - Bone loss
KW - Inflammation
KW - PPARγ
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U2 - 10.1093/gerona/glaa049
DO - 10.1093/gerona/glaa049
M3 - Article
C2 - 32060555
AN - SCOPUS:85083904553
SN - 1079-5006
VL - 75
SP - 826
EP - 834
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 5
ER -