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Biphasic and dosage-dependent regulation of osteoclastogenesis by β-catenin
Wei W; Zeve D; Suh JM; Wang X; Du Y(杜洋); Zerwekh JE; 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.
关键词Peroxisome Proliferator-activated Receptor  (Ppar)
DOI10.1128/MCB.05979-11
收录类别SCI
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被引频次:29[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/20493
专题中国科学院分子影像重点实验室
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Wei W,Zeve D,Suh JM,et al. Biphasic and dosage-dependent regulation of osteoclastogenesis by β-catenin[J]. Molecular and Cellular Biology,2011,31(23):4692.
APA Wei W.,Zeve D.,Suh JM.,Wang X.,Du Y.,...&Wan Y.(2011).Biphasic and dosage-dependent regulation of osteoclastogenesis by β-catenin.Molecular and Cellular Biology,31(23),4692.
MLA Wei W,et al."Biphasic and dosage-dependent regulation of osteoclastogenesis by β-catenin".Molecular and Cellular Biology 31.23(2011):4692.
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