{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:18:14Z","timestamp":1787239094483,"version":"build-2736575974"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T00:00:00Z","timestamp":1296691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interferon \u03b3 (IFN-\u03b3) is a cytokine produced locally in the bone microenvironment by cells of immune origin as well as mesenchymal stem cells. However, its role in normal bone remodeling is still poorly understood. In this study we first examined the consequences of IFN-\u03b3 ablation in vivo in C57BL\/6 mice expressing the IFN-\u03b3 receptor knockout phenotype (IFN\u03b3R1\u2212\/\u2212). Compared with their wild-type littermates (IFN\u03b3R1+\/+), IFN\u03b3R1\u2212\/\u2212 mice exhibit a reduction in bone volume associated with significant changes in cortical and trabecular structural parameters characteristic of an osteoporotic phenotype. Bone histomorphometry of IFN\u03b3R1\u2212\/\u2212 mice showed a low-bone-turnover pattern with a decrease in bone formation, a significant reduction in osteoblast and osteoclast numbers, and a reduction in circulating levels of bone-formation and bone-resorption markers. Furthermore, administration of IFN-\u03b3 (2000 and 10,000 units) to wild-type C57BL\/6 sham-operated (SHAM) and ovariectomized (OVX) female mice significantly improved bone mass and microarchitecture, mechanical properties of bone, and the ratio between bone formation and bone resorption in SHAM mice and rescued osteoporosis in OVX mice. These data therefore support an important physiologic role for IFN-\u03b3 signaling as a potential new anabolic therapeutic target for osteoporosis. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.350","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T09:47:27Z","timestamp":1296726447000},"page":"1472-1483","source":"Crossref","is-referenced-by-count":159,"title":["Interferon-\u03b3 plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice"],"prefix":"10.1093","volume":"26","author":[{"given":"Gustavo","family":"Duque","sequence":"first","affiliation":[{"name":"Ageing Bone Research Program, Sydney Medical School, The University of Sydney, Penrith, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao Chao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Bone and Periodontal Research, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Dion","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al, Research Center, H\u00f4pital Saint-Luc, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Macoritto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Bone and Periodontal Research, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rivas","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Ageing Bone Research Program, Sydney Medical School, The University of Sydney, Penrith, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian Fang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Bone and Periodontal Research, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Bone and Periodontal Research, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Bone and Periodontal Research, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faleh Tamim","family":"Marino","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Barralet","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viorica","family":"Lascau","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al, Research Center, H\u00f4pital Saint-Luc, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Desch\u00eanes","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al, Research Center, H\u00f4pital Saint-Luc, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis-Georges","family":"Ste-Marie","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al, Research Center, H\u00f4pital Saint-Luc, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Bone and Periodontal Research, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,2,3]]},"reference":[{"key":"2024020318024033600_bib1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0889-8529(02)00055-5","article-title":"Pathogenesis of osteoporosis","volume":"32","author":"Raisz","year":"2003","journal-title":"Endocrinol Metab Clin North Am."},{"key":"2024020318024033600_bib2","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s10875-009-9316-6","article-title":"Osteoimmunology: cross-talk between the immune and bone systems","volume":"29","author":"Nakashima","year":"2009","journal-title":"J Clin Immunol."},{"key":"2024020318024033600_bib3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1210\/er.2007-0038","article-title":"Osteoimmunology: interactions of the bone and immune system","volume":"29","author":"Lorenzo","year":"2008","journal-title":"Endocr Rev."},{"key":"2024020318024033600_bib4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.0105-2896.2005.00337.x","article-title":"Interplay between interferon and other cytokine systems in bone metabolism","volume":"208","author":"Takayanagi","year":"2005","journal-title":"Immunol Rev."},{"key":"2024020318024033600_bib5","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.4049\/jimmunol.0900072","article-title":"Inhibition of RANK expression and osteoclastogenesis by TLRs and IFN-\u03b3 in human osteoclast precursors","volume":"183","author":"Ji","year":"2009","journal-title":"J Immunol."},{"key":"2024020318024033600_bib6","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1074\/jbc.M804812200","article-title":"Interferon-gamma targets cancer cells and osteoclasts to prevent tumor-associated bone loss and bone metastases","volume":"284","author":"Xu","year":"2009","journal-title":"J Biol Chem."},{"key":"2024020318024033600_bib7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1172\/JCI30074","article-title":"IFN-\u03b3 stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation","volume":"117","author":"Gao","year":"2006","journal-title":"J Clin Invest."},{"key":"2024020318024033600_bib8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1138\/20060251","article-title":"Is IFN- Involved in Bone Loss or Protection? Nothing Is Simple With Cytokines","volume":"4","author":"Ferrari-Lacraz","year":"2007","journal-title":"BoneKEy-Osteovision."},{"key":"2024020318024033600_bib9","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1634\/stemcells.2008-0886","article-title":"Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role in early osteoblastogenesis","volume":"27","author":"Duque","year":"2009","journal-title":"Stem Cells."},{"key":"2024020318024033600_bib10","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/jcb.20933","article-title":"T-cell cytokine induction of BMP-2 regulates human mesenchymal stromal cell differentiation and mineralization","volume":"98","author":"Rifas","year":"2006","journal-title":"J Cell Biochem."},{"key":"2024020318024033600_bib11","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/gerona\/glp089","article-title":"Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice","volume":"64","author":"Rivas","year":"2009","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"2024020318024033600_bib12","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J Bone Miner Res."},{"key":"2024020318024033600_bib13","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","article-title":"Bone histomorphometry: Standardization of nomenclature, symbols and units","volume":"2","author":"Parfitt","year":"1987","journal-title":"J Bone Miner Res."},{"key":"2024020318024033600_bib14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/ar.1060","article-title":"Three-dimensional micro-imaging (MRmicroI and microCT), finite element modelling, and rapid prototyping provide unique insights into bone architecture in osteoporosis","volume":"265","author":"Borah","year":"2001","journal-title":"Anat Rec."},{"key":"2024020318024033600_bib15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cellbi.2008.09.012","article-title":"Combinatory responses of proinflamamtory cytokines on nitric oxide-mediated function in mouse calvarial osteoblasts","volume":"33","author":"Park","year":"2009","journal-title":"Cell Biol Int."},{"key":"2024020318024033600_bib16","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1111\/j.1532-5415.2008.01764.x","article-title":"Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome","volume":"56","author":"Duque","year":"2008","journal-title":"J Am Geriatr Soc."},{"key":"2024020318024033600_bib17","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.4049\/jimmunol.0900072","article-title":"Inhibition of RANK expression and osteoclastogenesis by TLRs and IFN-gamma in human osteoclast precursors","volume":"183","author":"Ji","year":"2009","journal-title":"J Immunol."},{"key":"2024020318024033600_bib18","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1097\/01.bor.0000231912.24740.a5","article-title":"Osteoclasts, rheumatoid arthritis, and osteoimmunology","volume":"18","author":"Sato","year":"2006","journal-title":"Curr Opin Rheumatol."},{"key":"2024020318024033600_bib19","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1126\/science.8456301","article-title":"Immune response in mice that lack the interferon-gamma receptor","volume":"259","author":"Huang","year":"1993","journal-title":"Science."},{"key":"2024020318024033600_bib20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-065X.1995.tb00090.x","article-title":"Immune defence in mice lacking type I and\/or type II interferon receptors","volume":"148","author":"Van den Broek","year":"1995","journal-title":"Immunol Rev."},{"key":"2024020318024033600_bib21","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1677\/joe.0.1700529","article-title":"Repeated in vivo determinations of bone mineral density during parathyroid hormone treatment in ovariectomized mice","volume":"170","author":"Andersson","year":"2001","journal-title":"J Endocrinol."},{"key":"2024020318024033600_bib22","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.bone.2006.01.145","article-title":"Combined treatment with a beta-blocker and intermittent PTH improves bone mass and microarchitecture in ovariectomized mice","volume":"39","author":"Pierroz","year":"2006","journal-title":"Bone."},{"key":"2024020318024033600_bib23","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0002-9440(10)63963-6","article-title":"Endothelial nitric oxide synthase gene-deficient mice demonstrate marked retardation in postnatal bone formation, reduced bone volume, and defects in osteoblast maturation and activity","volume":"158","author":"Aguirre","year":"2001","journal-title":"Am J Pathol."},{"key":"2024020318024033600_bib24","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1210\/endo.142.2.7977","article-title":"Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase","volume":"142","author":"Armour","year":"2001","journal-title":"Endocrinology."},{"key":"2024020318024033600_bib25","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1210\/endo.135.1.7516867","article-title":"Human osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase","volume":"135","author":"Ralston","year":"1994","journal-title":"Endocrinology."},{"key":"2024020318024033600_bib26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1046\/j.1365-2567.2001.01261.x","article-title":"Nitric oxide and bone","volume":"103","author":"Van't Hof","year":"2001","journal-title":"Immunology."},{"key":"2024020318024033600_bib27","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1096\/fasebj.14.3.523","article-title":"Best5: a novel interferon-inducible gene expressed during bone formation","volume":"14","author":"Grewal","year":"2000","journal-title":"FASEB J."},{"key":"2024020318024033600_bib28","doi-asserted-by":"crossref","first-page":"27743","DOI":"10.1074\/jbc.M314323200","article-title":"Stat1 controls postnatal bone formation by regulating fibroblast growth factor signaling in osteoblasts","volume":"279","author":"Xiao","year":"2004","journal-title":"J Biol Chem."},{"key":"2024020318024033600_bib29","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1101\/gad.1119303","article-title":"Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation","volume":"17","author":"Kim","year":"2003","journal-title":"Genes Dev."},{"key":"2024020318024033600_bib30","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1016\/j.yexcr.2009.02.003","article-title":"PKR-mediated degradation of STAT1 regulates osteoblast differentiation","volume":"315","author":"Yoshida","year":"2009","journal-title":"Exp Cell Res."},{"key":"2024020318024033600_bib31","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1172\/JCI1333","article-title":"Interleukin 18 inhibits osteoclast formation via T cell production of granulocyte macrophage colony-stimulating factor","volume":"101","author":"Horwood","year":"1998","journal-title":"J Clin Invest."},{"key":"2024020318024033600_bib32","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/35046102","article-title":"T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma","volume":"408","author":"Takayanagi","year":"2000","journal-title":"Nature."},{"key":"2024020318024033600_bib33","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1210\/en.2002-220597","article-title":"Inducible nitric oxide synthase mediates bone loss in ovariectomized mice","volume":"144","author":"Cuzzocrea","year":"2003","journal-title":"Endocrinology."},{"key":"2024020318024033600_bib34","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.0105-2896.2005.00324.x","article-title":"The role of T lymphocytes in bone metabolism","volume":"208","author":"Weitzmann","year":"2005","journal-title":"Immunol Rev."},{"key":"2024020318024033600_bib35","doi-asserted-by":"crossref","first-page":"10405","DOI":"10.1073\/pnas.1533207100","article-title":"Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator","volume":"100","author":"Cenci","year":"2003","journal-title":"Proc Natl Acad Sci USA."},{"key":"2024020318024033600_bib36","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/humrep\/dei413","article-title":"Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice","volume":"21","author":"Garc\u00eda-P\u00e9rez","year":"2006","journal-title":"Hum Reprod."},{"key":"2024020318024033600_bib37","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1359\/jbmr.2003.18.7.1206","article-title":"Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice","volume":"18","author":"Sun","year":"2003","journal-title":"J Bone Miner Res."},{"key":"2024020318024033600_bib38","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0015-0282(00)00622-1","article-title":"Hormone replacement therapy reverses the decrease in natural killer cytotoxicity but does not reverse the decreases in the T-cell subpopulation or interferon-gamma production in postmenopausal women","volume":"74","author":"Yang","year":"2000","journal-title":"Fertil Steril."},{"key":"2024020318024033600_bib39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jri.2004.02.001","article-title":"Immune effects of surgical menopause and estrogen replacement therapy in peri-menopausal women","volume":"63","author":"Kumru","year":"2004","journal-title":"J Reprod Immunol."},{"key":"2024020318024033600_bib40","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.4049\/jimmunol.145.10.3209","article-title":"Unusual T cell populations in adult murine bone marrow. Prevalence of CD3+CD4-CD8- and alpha beta TCR+NK1.1+ cells","volume":"145","author":"Sykes","year":"1990","journal-title":"J Immunol."},{"key":"2024020318024033600_bib41","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1385\/JCD:7:3:326","article-title":"Accuracy and precision of PIXImus densitometry for ex vivo mouse long bones: comparison of technique and software version","volume":"7","author":"Lopez Franco","year":"2004","journal-title":"J Clin Densitom."},{"key":"2024020318024033600_bib42","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1210\/en.2004-1642","article-title":"Mathematical model of paracrine interactions between osteoclasts and osteoblasts predicts anabolic action of parathyroid hormone on bone","volume":"146","author":"Komarova","year":"2005","journal-title":"Endocrinology."},{"key":"2024020318024033600_bib43","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tem.2004.01.006","article-title":"Parathyroid hormone: a double-edged sword for bone metabolism","volume":"15","author":"Qin","year":"2004","journal-title":"Trends Endocrinol Metab."},{"key":"2024020318024033600_bib44","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/BF01533380","article-title":"Comparative study of inhibitory effects by murine interferon gamma and a new bisphosphonate (alendronate) in hypercalcemic, nude mice bearing human tumor (LJC-1-JCK)","volume":"39","author":"Tohkin","year":"1994","journal-title":"Cancer Immunol Immunother."},{"key":"2024020318024033600_bib45","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1210\/endo.135.3.8070349","article-title":"Interferon-gamma causes loss of bone volume in vivo and fails to ameliorate cyclosporin A-induced osteopenia","volume":"135","author":"Mann","year":"1994","journal-title":"Endocrinology."},{"key":"2024020318024033600_bib46","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1056\/NEJM199506153322402","article-title":"Long-term treatment of osteopetrosis with recombinant human interferon gamma","volume":"332","author":"Key","year":"1995","journal-title":"N Engl J Med."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.350","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/7\/1472\/56559188\/350_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/7\/1472\/56559188\/350_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T11:02:06Z","timestamp":1710327726000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/26\/7\/1472-1483\/7598130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,3]]},"references-count":46,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2011,2,3]]},"published-print":{"date-parts":[[2011,7,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.350","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,7,1]]},"published":{"date-parts":[[2011,2,3]]}}}