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Title: Osteoimmunological investigations of bone mineral density in a mouse model : in vivo and in vitro study
Author: Saeed, Zeayd F. S.
ISNI:       0000 0004 7970 2944
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2019
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Bone mineral density (BMD) is affected by complement system activation, excessive lipoproteins. One purpose of this project was to investigate the effect of complement properdin, the only positive complement regulator, on bone mineral density and the osteoclasts participation in alternative pathway component production. In vivo assays showed that there was no significant alteration in bone mineral density in properdin knockout (PKO) mice and wildtype at six months of age, and in vitro, the osteoclasts number and resorptive activity were the same in both genotypes, but there was a significant increase in BMD of PKO at an older age (10 months). Also, osteoclasts contribute to complement components production of CFD, CFB, CFP and C3 but not C5 and Vitamin D3 may have a role in curbing excessive complement component production by osteoclast induced by fatty acid. Hereditary hypertriglyceridemia have an adverse effect on bone mineral density. Therefore, an additional aim of this project was to investigate the role of dietary supplementation of Vitamin D3 on BMD reduction induced by Low density lipoprotein receptor knockout (LDLR-/-) mice. The in vivo investigation showed that Vitamin D3 normalise the BMD reduction induced by LDLR-/- mice by enhancing osteoblast activity and reducing osteoclast activity. In vitro assays indicated that Vitamin D3 has an essential action on lowering osteoclast resorptive activity or enhancing osteoblast mineral deposition in LDLR-/- cell culture. In addition, Vitamin D3 has an anti-inflammatory action by normalising the secretion of tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) cytokines in vivo. In conclusion, these findings show that complement properdin could have a role in BMD at more advanced ages, and the osteoclasts may contribute in alternative complement components expression. Vitamin D3 normalise bone mineral density reduction in LDLR-/-.
Supervisor: Stover, Cordula ; Barratt, Jonathan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available