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Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population
Wei W; Zeve D; Wang X; Du Y(杜洋); Tang W; Dechow PC; Graff JM; Wan Y
2011-12
发表期刊Molecular and Cellular Biology
卷号31期号:23页码:4692
摘要

Osteoclasts are bone-resorbing cells essential for skeletal development, homeostasis, and regeneration. They derive from hematopoietic progenitors in the monocyte/macrophage lineage and differentiate in response to RANKL. However, the precise nature of osteoclast progenitors is a longstanding and important question. Using inducible peroxisome proliferator-activated receptor γ (PPARγ)-tTA TRE-GFP (green fluorescent protein) reporter mice, we show that osteoclast progenitors reside specifically in the PPARγ-expressing hematopoietic bone marrow population and identify the quiescent PPARγ(+) cells as osteoclast progenitors. Importantly, two PPARγ-tTA TRE-Cre-controlled genetic models provide compelling functional evidence. First, Notch activation in PPARγ(+) cells causes high bone mass due to impaired osteoclast precursor proliferation. Second, selective ablation of PPARγ(+) cells by diphtheria toxin also causes high bone mass due to decreased osteoclast numbers. Furthermore, PPARγ(+) cells respond to both pathological and pharmacological resorption-enhancing stimuli. Mechanistically, PPARγ promotes osteoclast progenitors by activating GATA2 transcription. These findings not only identify the long-sought-after osteoclast progenitors but also establish unprecedented tools for their visualization, isolation, characterization, and genetic manipulation.

PMID:
 
21947280
 
PMCID:
 
PMC3232921
 
DOI:
 
10.1128/MCB.05979-11
关键词Osteoclasts Ppar
收录类别SCI
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/20494
专题中国科学院分子影像重点实验室
推荐引用方式
GB/T 7714
Wei W,Zeve D,Wang X,et al. Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population[J]. Molecular and Cellular Biology,2011,31(23):4692.
APA Wei W.,Zeve D.,Wang X.,Du Y.,Tang W.,...&Wan Y.(2011).Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population.Molecular and Cellular Biology,31(23),4692.
MLA Wei W,et al."Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population".Molecular and Cellular Biology 31.23(2011):4692.
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