Death receptor 3 (TNFRSF25) increases mineral apposition by osteoblasts and region specific new bone formation in the axial skeleton of male DBA/1 mice

Fraser L. Collins, Jessica O. Williams, Anja C. Bloom, Michael D. Stone, Ernest Choy, Eddie C.Y. Wang, Anwen S. Williams

Research output: Contribution to journalArticle

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Abstract

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 ( DR3ko ) and wild-type ( DR3wt ) 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 DR3wt mice. Alkaline phosphatase, osteopontin, and mineral apposition were significantly elevated in DR3wt cultures. Levels of RANKL were comparable whilst osteoprotegerin was significantly increased in DR3wt cultures. In vivo incorporation of BoneTag was significantly lower in the thoracic vertebrae of 10-month-old DR3ko 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.
Original languageEnglish
Article number901679
Number of pages9
JournalJournal of Immunology Research
Volume2015
DOIs
Publication statusPublished - 2015

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Receptors, Tumor Necrosis Factor, Member 25
Inbred DBA Mouse
Osteoblasts
Osteogenesis
Skeleton
Minerals
Osteoprotegerin
Osteopontin
Alkaline Phosphatase
Thoracic Vertebrae
Genome-Wide Association Study
Ankylosing Spondylitis
Matrix Metalloproteinases
Fluorescent Dyes
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Pathology
Ligands
Bone and Bones
Proteins

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Death receptor 3 (TNFRSF25) increases mineral apposition by osteoblasts and region specific new bone formation in the axial skeleton of male DBA/1 mice. / Collins, Fraser L.; Williams, Jessica O.; Bloom, Anja C.; Stone, Michael D.; Choy, Ernest; Wang, Eddie C.Y.; Williams, Anwen S.

In: Journal of Immunology Research, Vol. 2015, 901679, 2015.

Research output: Contribution to journalArticle

Collins, Fraser L. ; Williams, Jessica O. ; Bloom, Anja C. ; Stone, Michael D. ; Choy, Ernest ; Wang, Eddie C.Y. ; Williams, Anwen S. / Death receptor 3 (TNFRSF25) increases mineral apposition by osteoblasts and region specific new bone formation in the axial skeleton of male DBA/1 mice. In: Journal of Immunology Research. 2015 ; Vol. 2015.
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abstract = "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 ( DR3ko ) and wild-type ( DR3wt ) 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 DR3wt mice. Alkaline phosphatase, osteopontin, and mineral apposition were significantly elevated in DR3wt cultures. Levels of RANKL were comparable whilst osteoprotegerin was significantly increased in DR3wt cultures. In vivo incorporation of BoneTag was significantly lower in the thoracic vertebrae of 10-month-old DR3ko 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.",
author = "Collins, {Fraser L.} and Williams, {Jessica O.} and Bloom, {Anja C.} and Stone, {Michael D.} and Ernest Choy and Wang, {Eddie C.Y.} and Williams, {Anwen S.}",
note = "Fraser L. Collins and this work were funded by an Arthritis Research UK PhD studentship (Grant Code: 18598) awarded to Anwen S. Williams, Eddie C. Y. Wang, and Michael D. Stone. Eddie C. Y. Wang was additionally funded by MRC Project Grant G0901119. Funding for open access was kindly provided by Cardiff University.",
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T1 - Death receptor 3 (TNFRSF25) increases mineral apposition by osteoblasts and region specific new bone formation in the axial skeleton of male DBA/1 mice

AU - Collins, Fraser L.

AU - Williams, Jessica O.

AU - Bloom, Anja C.

AU - Stone, Michael D.

AU - Choy, Ernest

AU - Wang, Eddie C.Y.

AU - Williams, Anwen S.

N1 - Fraser L. Collins and this work were funded by an Arthritis Research UK PhD studentship (Grant Code: 18598) awarded to Anwen S. Williams, Eddie C. Y. Wang, and Michael D. Stone. Eddie C. Y. Wang was additionally funded by MRC Project Grant G0901119. Funding for open access was kindly provided by Cardiff University.

PY - 2015

Y1 - 2015

N2 - 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 ( DR3ko ) and wild-type ( DR3wt ) 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 DR3wt mice. Alkaline phosphatase, osteopontin, and mineral apposition were significantly elevated in DR3wt cultures. Levels of RANKL were comparable whilst osteoprotegerin was significantly increased in DR3wt cultures. In vivo incorporation of BoneTag was significantly lower in the thoracic vertebrae of 10-month-old DR3ko 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.

AB - 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 ( DR3ko ) and wild-type ( DR3wt ) 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 DR3wt mice. Alkaline phosphatase, osteopontin, and mineral apposition were significantly elevated in DR3wt cultures. Levels of RANKL were comparable whilst osteoprotegerin was significantly increased in DR3wt cultures. In vivo incorporation of BoneTag was significantly lower in the thoracic vertebrae of 10-month-old DR3ko 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.

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