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Title 

The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors

Authors 

O H KwonC K LeeYoung Ik LeeS G PaikHyun Jun Lee

Publisher 

Elsevier

Issue Date 

2005

Citation 

Biochemical and Biophysical Research Communications, vol. 335, no. 2, pp. 437-446

Keywords 

differentiationhematopoiesisM-CSFosteoclastpromoterPU.1RANKtranscription factorcolony stimulating factorosteoclast differentiation factor

Abstract 

Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor κB (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1-/- progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2005.07.092

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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