Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

CD59a – A novel role in bone

Bloom, Anja Constanze 2012. CD59a – A novel role in bone. PhD Thesis, Cardiff University.
Item availability restricted.

[img]
Preview
PDF - Accepted Post-Print Version
Download (10MB) | Preview
[img] PDF - Supplemental Material
Restricted to Repository staff only

Download (116kB)

Abstract

The complement system has crucial functions in host defence. Novel data revealed a role for complement components in the pathology of osteoarthritis (OA). CD59a is a regulator of the terminal complement pathway in mice; the purpose of the study was to determine if CD59a-/- mice have an osteoarthritic bone phenotype. Osteoblast (OB) mineralisation, colony forming unit (CFU) and OCG assays were performed in vitro from bone marrow preparations of 8-20 week old mice. Decreased CFU differentiating towards osteoblasts and adipocytes (n=1 only), as well as an increased OCG, was revealed in male CD59a deficient (-/-) over wildtype (WT) mice. OCG in females were comparable. A human CD59 knockdown system utilising short hairpin (sh) ribonucleic acid (RNA) delivered by adenoviruses was established but did not differentiate into osteoclasts (OC). In vivo the bone phenotype of CD59a-/- mice was established for femora and vertebra L6 via X-ray, microcomputed tomography and histology. In male mice femoral length was increased in CD59a-/- versus WT mice at 8-10, 20 and 50 weeks. Cortical bone volume was increased whilst bone mineral density (BMD) was reduced in CD59a-/- versus WT mice at 8-10 and 20 weeks. Trabecular bone analysis of the distal femur (and spine) showed increased trabecular bone ratio, number, thickness, connectivity and total BMD in CD59a-/- over WT at 8-10 (and 20) weeks of age. In female mice there was no difference in femoral length and trabecular bone, but cortical BMD was raised at 50 weeks (CD59a-/- versus WT). Finally, histology revealed enhanced mineral apposition rate and OC surface as well as reduced osteoid surface in male CD59a-/- over WT mice at 8-10 weeks of age. Increased bone growth and turnover related to CD59a gene deletion were gender specific. These studies highlight CD59a as a potential target for OA treatment.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RB Pathology
Uncontrolled Keywords: CD59a ; mouse ; bone ; MicroCT ; osteoclastogenesis
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:07
URI: http://orca.cardiff.ac.uk/id/eprint/39661

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics