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2015 ; 2015
(ä): 901679
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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
#MMPMID26065008
Collins FL
; Williams JO
; Bloom AC
; Stone MD
; Choy E
; Wang EC
; Williams AS
J Immunol Res
2015[]; 2015
(ä): 901679
PMID26065008
show ga
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 (DR3(ko)) and wild-type (DR3(wt)) 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
DR3(wt) mice. Alkaline phosphatase, osteopontin, and mineral apposition were
significantly elevated in DR3(wt) cultures. Levels of RANKL were comparable
whilst osteoprotegerin was significantly increased in DR3(wt) cultures. In vivo
incorporation of BoneTag was significantly lower in the thoracic vertebrae of
10-month-old DR3(ko) 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.