{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T01:47:22Z","timestamp":1776822442302,"version":"3.51.2"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["18598"],"award-info":[{"award-number":["18598"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["G0901119"],"award-info":[{"award-number":["G0901119"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC Project","award":["18598"],"award-info":[{"award-number":["18598"]}]},{"name":"MRC Project","award":["G0901119"],"award-info":[{"award-number":["G0901119"]}]},{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"publisher","award":["18598"],"award-info":[{"award-number":["18598"]}],"id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"publisher","award":["G0901119"],"award-info":[{"award-number":["G0901119"]}],"id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p><jats:italic>Objectives<\/jats:italic>. Genome wide association studies identified TNFSF member TNF-like protein 1A (TL1A, TNFSF15) as a potential modulator of ankylosing spondylitis (AS). TL1A is the only confirmed TNFSF ligand of death receptor 3 (DR3, TNFRSF25); however, its role in disease pathology is not characterised. We evaluated DR3\u2019s role in controlling osteoblast- (OB-) dependent bone formation<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>.<jats:italic>Methods<\/jats:italic>. Osteoprogenitor cells and OB were cultured from male DR3-deficient (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mtext>DR<\/mml:mtext><mml:msup><mml:mrow><mml:mn mathvariant=\"normal\">3<\/mml:mn><\/mml:mrow><mml:mrow><mml:mtext>ko<\/mml:mtext><\/mml:mrow><\/mml:msup><\/mml:math>) and wild-type (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mtext>DR<\/mml:mtext><mml:msup><mml:mrow><mml:mn mathvariant=\"normal\">3<\/mml:mn><\/mml:mrow><mml:mrow><mml:mtext>wt<\/mml:mtext><\/mml:mrow><\/mml:msup><\/mml:math>) DBA\/1 mice. DR3 and RANKL expression were tested by flow cytometry. Alkaline phosphatase and mineralization were quantified. Osteopontin, osteoprotegerin, and pro MMP-9 were measured by ELISA. A fluorescent probe (BoneTag) was used to measure<jats:italic>in vivo<\/jats:italic>mineralization in 10-month-old mice.<jats:italic>Results<\/jats:italic>. DR3 was expressed on osteoprogenitors and OB from<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mtext>DR<\/mml:mtext><mml:msup><mml:mrow><mml:mn mathvariant=\"normal\">3<\/mml:mn><\/mml:mrow><mml:mrow><mml:mtext>wt<\/mml:mtext><\/mml:mrow><\/mml:msup><\/mml:math>mice. Alkaline phosphatase, osteopontin, and mineral apposition were significantly elevated in<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mtext>DR<\/mml:mtext><mml:msup><mml:mrow><mml:mn mathvariant=\"normal\">3<\/mml:mn><\/mml:mrow><mml:mrow><mml:mtext>wt<\/mml:mtext><\/mml:mrow><\/mml:msup><\/mml:math>cultures. Levels of RANKL were comparable whilst osteoprotegerin was significantly increased in<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mtext>DR<\/mml:mtext><mml:msup><mml:mrow><mml:mn mathvariant=\"normal\">3<\/mml:mn><\/mml:mrow><mml:mrow><mml:mtext>wt<\/mml:mtext><\/mml:mrow><\/mml:msup><\/mml:math>cultures.<jats:italic>In vivo<\/jats:italic>incorporation of BoneTag was significantly lower in the thoracic vertebrae of 10-month-old<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mtext>DR<\/mml:mtext><mml:msup><mml:mrow><mml:mn mathvariant=\"normal\">3<\/mml:mn><\/mml:mrow><mml:mrow><mml:mtext>ko<\/mml:mtext><\/mml:mrow><\/mml:msup><\/mml:math>mice.<jats:italic>Conclusions<\/jats:italic>. These data identify new roles for DR3 in regulating OB-dependent bone mineral apposition. They potentially begin to explain the atypical pattern of new bone formation observed in the axial skeleton of grouped, aging DBA\/1 mice.<\/jats:p>","DOI":"10.1155\/2015\/901679","type":"journal-article","created":{"date-parts":[[2015,5,3]],"date-time":"2015-05-03T17:05:35Z","timestamp":1430672735000},"page":"1-9","source":"Crossref","is-referenced-by-count":13,"title":["Death Receptor 3 (TNFRSF25) Increases Mineral Apposition by Osteoblasts and Region Specific New Bone Formation in the Axial Skeleton of Male DBA\/1 Mice"],"prefix":"10.1155","volume":"2015","author":[{"given":"Fraser L.","family":"Collins","sequence":"first","affiliation":[{"name":"Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica O.","family":"Williams","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja C.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Stone","sequence":"additional","affiliation":[{"name":"University Hospital Llandough, Cardiff & Vale University Health Board, Cardiff CF64 2XX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest","family":"Choy","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eddie C. 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