Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population

W. Wei, Daniel Zeve, Xueqian Wang, Yang Du, Wei Tang, Paul C. Dechow, Jonathan M. Graff, Yihong Wan

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4692-4705
Number of pages14
JournalMolecular and Cellular Biology
Volume31
Issue number23
DOIs
StatePublished - Dec 2011

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Peroxisome Proliferator-Activated Receptors
Osteoclasts
Bone Marrow Cells
Population
Bone and Bones
Diphtheria Toxin
Genetic Models
Green Fluorescent Proteins
Regeneration
Monocytes
Homeostasis
Bone Marrow
Macrophages
Pharmacology

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population. / Wei, W.; Zeve, Daniel; Wang, Xueqian; Du, Yang; Tang, Wei; Dechow, Paul C.; Graff, Jonathan M.; Wan, Yihong.

In: Molecular and Cellular Biology, Vol. 31, No. 23, 12.2011, p. 4692-4705.

Research output: Contribution to journalArticle

Wei, W. ; Zeve, Daniel ; Wang, Xueqian ; Du, Yang ; Tang, Wei ; Dechow, Paul C. ; Graff, Jonathan M. ; Wan, Yihong. / Osteoclast progenitors reside in the peroxisome proliferator-activated receptor γ-expressing bone marrow cell population. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 23. pp. 4692-4705.
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