The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors
- Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Oun-dong, Yusong, Daejeon 305-333 (Korea, Republic of)
- College of Pharmacy, Chungbuk National University (Korea, Republic of)
- Liver Cell Signal Transduction Laboratory, Korea Research Institute of Bioscience and Biotechnology, 52 Oun-dong, Yusong, Daejeon 305-333 (Korea, Republic of)
- Department of Biology, School of Bioscience and Biotechnology, Chungnam National University (Korea, Republic of)
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 {kappa}B (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1 {sup -/-} 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.
- OSTI ID:
- 20710980
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 335, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2005.07.092; PII: S0006-291X(05)01567-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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