Stat1-mediated cytoplasmic attenuation in osteoimmunology
Signal transducer and activator of transcription 1 (Stat1) is a critical mediator of gene transcription in type I interferon (IFN‐α/β) signaling that is essential for host defense against viruses. In the skeletal system, type I IFNs (IFN‐α/β) also play an important physiological role in the inhibiti...
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Published in | Journal of cellular biochemistry Vol. 94; no. 2; pp. 232 - 240 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.02.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Signal transducer and activator of transcription 1 (Stat1) is a critical mediator of gene transcription in type I interferon (IFN‐α/β) signaling that is essential for host defense against viruses. In the skeletal system, type I IFNs (IFN‐α/β) also play an important physiological role in the inhibition of receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast differentiation and bone resorption: mice deficient in IFN signaling exhibit decreased bone mass accompanied by the activation of osteoclastogenesis. On the other hand, an unexpected increase in bone mass was observed in Stat1‐deficient mice, indicating that Stat1 has a hitherto unknown function in the regulation of bone formation. Indeed, Stat1 was found to have a unique, non‐canonical function as a cytoplasmic attenuator of Runx2, a key transcription factor for osteoblast differentiation. Thus, the loss of Stat1 results in excessive activation of Runx2 and osteoblast differentiation, thereby tipping the balance in favor of bone formation over bone resorption. This is an interesting example in which a latent transcription factor attenuates the activity of another transcription factor in the cytoplasm, and reveals a novel regulatory mechanism of bone remodeling by immunomodulatory molecules. Here, we summarize recent advances in the study of Stat1 and IFNs in the context of osteoimmunology, including latest reports that question whether the inhibitory function of Stat1 in chondrocytes is responsible for dwarfism in achondroplasia. © 2004 Wiley‐Liss, Inc. |
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Bibliography: | Mitsubishi Foundation Ministry of Health, Labour and Welfare of Japan The Kato Trust for Nanbyo Research istex:7D5F701B9A79C50743538687C4F06C4FDCDD846B Takeda Science Foundation The 21st century COE program 'Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone' ArticleID:JCB20316 Ministry of Education, Culture, Sports, Science, and Technology of Japan The PRESTO program of JST ark:/67375/WNG-0R52JSPH-G ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 0730-2312 1097-4644 |
DOI: | 10.1002/jcb.20316 |