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Journal of Immunology Research
Volume 2015, Article ID 901679, 9 pages
Research Article

Death Receptor 3 (TNFRSF25) Increases Mineral Apposition by Osteoblasts and Region Specific New Bone Formation in the Axial Skeleton of Male DBA/1 Mice

1Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
2University Hospital Llandough, Cardiff & Vale University Health Board, Cardiff CF64 2XX, UK

Received 17 October 2014; Revised 1 December 2014; Accepted 1 December 2014

Academic Editor: Giacomina Brunetti

Copyright © 2015 Fraser L. Collins et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objectives. 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’s role in controlling osteoblast- (OB-) dependent bone formation in vitro and in vivo. Methods. Osteoprogenitor cells and OB were cultured from male DR3-deficient () and wild-type () 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 in vivo mineralization in 10-month-old mice. Results. DR3 was expressed on osteoprogenitors and OB from mice. Alkaline phosphatase, osteopontin, and mineral apposition were significantly elevated in cultures. Levels of RANKL were comparable whilst osteoprotegerin was significantly increased in cultures. In vivo incorporation of BoneTag was significantly lower in the thoracic vertebrae of 10-month-old mice. Conclusions. 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.