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Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice

Bloom, Anja C., Collins, Fraser L., van't Hof, Rob J., Ryan, Elizabeth S., Jones, Emma, Hughes, Timothy R.

, Morgan, B. Paul

, Erlandsson, Malin, Bokarewa, Maria, Aeschlimann, Daniel

, Evans, Bronwen A. J.

and Williams, Anwen S.

2016. Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice. Bone 84 , pp. 253-261. 10.1016/j.bone.2015.12.014

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Official URL: http://dx.doi.org/10.1016/j.bone.2015.12.014

Abstract

Degenerative joint diseases such as osteoarthritis are characterised by aberrant region-specific bone formation and abnormal bone mineral content. A recent study suggested a role for the complement membrane attack complex in experimental models of osteoarthritis. Since CD59a is the principal regulator of the membrane attack complex in mice, we evaluated the impact of CD59a gene deletion upon maintenance of bone architecture. In vivo bone morphology analysis revealed that male CD59a-deficient mice have increased femur length and cortical bone volume, albeit with reduced bone mineral density. However, this phenomenon was not observed in female mice. Histomorphometric analysis of the trabecular bone showed increased rates of bone homeostasis, with both increased bone resorption and mineral apposition rate in CD59a-deficient male mice. When bone cells were studied in isolation, in vitro osteoclastogenesis was significantly increased in male CD59a-deficient mice, although osteoblast formation was not altered. Our data reveal, for the first time, that CD59a is a regulator of bone growth and homeostasis. CD59a ablation in male mice results in longer and wider bones, but with less density, which is likely a major contributing factor for their susceptibility to osteoarthritis. These findings increase our understanding of the role of complement regulation in degenerative arthritis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Medicine
Additional Information:	This is an open access article under the CC BY license.
Publisher:	Elsevier
ISSN:	8756-3282
Funders:	Arthritis Research UK, Cardiff University PhD studentship
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	21 December 2015
Last Modified:	11 Oct 2023 21:54
URI:	https://orca.cardiff.ac.uk/id/eprint/84407