A novel role for interferon regulatory factor 1 (IRF1) in regulation of bone metabolism. Issue 8 (20th June 2014)

• Record Type: Journal Article
• Authors: Salem, Sandra; Gao, Chan; Li, Ailian; Wang, Huifen; Nguyen‐Yamamoto, Loan; Goltzman, David; Henderson, Janet E.; Gros, Philippe
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 8(2014)
• Page Start: 1588
• Page End: 1598
• Publication Date: 2014-06-20
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12327
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12327-abs-0001"> <title>Abstract</title> <p>Increased risk of bone fractures is observed in patients with chronic inflammatory conditions, such as inflammatory bowel disease and rheumatoid arthritis. Members of the Interferon Response Factor family of transcriptional regulators, IRF1 and IRF8, have been identified as genetic risk factors for several chronic inflammatory and autoimmune diseases. We have investigated a potential role for the <italic>Irf1</italic> gene in bone metabolism. Here, we report that <italic>Irf1</italic><sup><italic>−/−</italic></sup>mutant mice show altered bone morphology in association with altered trabecular bone architecture and increased cortical thickness and cellularity. <italic>Ex vivo</italic> studies on cells derived from bone marrow stimulated with Rank ligand revealed an increase in size and resorptive activity of tartrate‐resistant acid‐positive cells from <italic>Irf1</italic><sup><italic>−/−</italic></sup> mutant mice compared with wild‐type control mice. <italic>Irf1</italic> deficiency was also associated with decreased proliferation of bone marrow‐derived osteoblast precursors <italic>ex vivo</italic>, concomitant with increased mineralization activity compared with control cells. We show that Irf1 plays a role in bone metabolism and suggest that Irf1 regulates the maturation and activity of osteoclasts and osteoblasts. The altered bone phenotype of <italic>Irf1</italic><sup><italic>−/−</italic></sup> mutants is strikingly similar to that of <italic>Stat1</italic><sup><italic>−/−</italic></sup> mice, suggesting that the two interacting proteins play a critical enabling role in the common regulation of these two cell lineages.</p> </abstract>