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Deletion of PPARγ in Mesenchymal Lineage Cells Protects Against Aging-Induced Cortical Bone Loss in Mice.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences ( IF 5.1 ) Pub Date : 2020-04-17 , DOI: 10.1093/gerona/glaa049
Jay Cao 1 , Kehong Ding 2, 3 , Guodong Pan 3 , Raysa Rosario 3 , Yun Su 2, 3 , Yonggang Bao 3 , Hongyan Zhou 3 , Jianru Xu 2, 3 , Meghan E McGee Lawrence 2, 4 , Mark W Hamrick 2, 4 , Carlos M Isales 2, 3, 5 , Xingming Shi 2, 3, 5
Affiliation  

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.

中文翻译:

间充质谱系细胞中PPARγ的删除可防止衰老引起的小鼠皮质骨丢失。

衰老中的骨质流失与慢性低度炎症和动物和人类骨髓脂肪的积累有关。过氧化物酶体增殖物激活受体γ(PPARγ),一种成脂调节剂,在这些生物学过程中起关键作用。但是,缺乏关于PPARγ在与年龄有关的骨质流失和炎症中的作用的研究。我们假设,骨髓间充质谱系细胞中PPARγ的缺失将减少衰老引起的骨丢失,这可能是通过减少脂肪产生的炎症反应和增加成骨细胞活性来实现的。在本研究中,我们显示了在表达Dermo1的间充质谱系细胞(Dermo1-Cre:PPARγfl / fl)减少了脂肪,增加了皮质骨的厚度,但PPARγ的缺乏对小梁骨的保护作用受到了限制,如双能X射线吸收法,μCT和组织形态分析所证实。有条件地敲除PPARγ可降低血清脂联素的浓度,包括脂联素,抵抗素和瘦素,并降低炎症相关基因的骨髓基质细胞表达水平。干扰素信号传导途径中涉及的炎症基因减少最多。这些结果表明,破坏主脂肪形成调节剂PPARγ对衰老引起的骨质流失具有一定的保护作用,
更新日期:2020-04-18
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