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http://purl.uniprot.org/citations/31299941http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31299941http://www.w3.org/2000/01/rdf-schema#comment"

Background

Oestrogen-deficiency induced by menopause is associated with reduced bone density and primary osteoporosis, resulting in an increased risk of fracture. While the exact etiology of menopause-induced primary osteoporotic bone loss is not fully known, members of the tumour necrosis factor super family (TNFSF) are known to play a role. Recent studies have revealed that the TNFSF members death receptor 3 (DR3) and one of its ligands, TNF-like protein 1A (TL1A) have a key role in secondary osteoporosis; enhancing CD14+ peripheral blood mononuclear cell (PBMC) osteoclast formation and bone resorption. Whether DR3 and TL1A contribute towards bone loss in menopause-induced primary osteoporosis however, remains unknown.

Methods

To investigate this we performed flow cytometry analysis of DR3 expression on CD14+ PBMCs isolated from pre- and early post-menopausal females and late post-menopausal osteoporotic patients. Serum levels of TL1A, CCL3 and total MMP-9 were measured by ELISA. In vitro osteoclast differentiation assays were performed to determine CD14+ monocyte osteoclastogenic potential. In addition, splenic CD4+ T cell DR3 expression was investigated 1 week and 8 weeks post-surgery, using the murine ovariectomy model.

Results

In contrast to pre-menopausal females, CD14+ monocytes isolated from post-menopausal females were unable to induce DR3 expression. Serum TL1A levels were decreased approx. 2-fold in early post-menopausal females compared to pre-menopausal controls and post-menopausal osteoporotic females; no difference was observed between pre-menopausal and late post-menopausal osteoporotic females. Analysis of in vitro CD14+ monocyte osteoclastogenic potential revealed no significant difference between the post-menopausal and post-menopausal osteoporotic cohorts. Interestingly, in the murine ovariectomy model splenic CD4+ T cell DR3 expression was significantly increased at 1 week but not 8 weeks post-surgery when compared to the sham control.

Conclusion

Our results reveals for the first time that loss of oestrogen has a significant effect on DR3; decreasing expression on CD14+ monocytes and increasing expression on CD4+ T cells. These data suggest that while oestrogen-deficiency induced changes in DR3 expression do not affect late post-menopausal bone loss they could potentially have an indirect role in early menopausal bone loss through the modulation of T cell activity."xsd:string
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http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/author"Turton J."xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/author"Stone M.D."xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/author"Williams A.S."xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/author"Wang E.C.Y."xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/author"McCabe L.R."xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/author"Collins F.L."xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/name"BMC Musculoskelet Disord"xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/pages"326"xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/title"Oestrogen-deficiency induces bone loss by modulating CD14+ monocyte and CD4+ T cell DR3 expression and serum TL1A levels."xsd:string
http://purl.uniprot.org/citations/31299941http://purl.uniprot.org/core/volume"20"xsd:string
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