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
et al (show 2 more authors) (2016) Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice. Bone, 84. 253 - 261.

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Abstract

Degenerative joint diseases such as osteoarthritis are characterised by aberrant region-specificboneformationand abnormal bone mineral content. A recent study suggested a role for the complement membrane attack com-plex in experimental models of osteoarthritis. Since CD59a is the principal regulator of the membrane attackcomplex in mice, we evaluated the impact of CD59a gene deletion upon maintenance of bone architecture.In vivobone morphology analysis revealed that male CD59a-deficient mice have increased femur length and cor-tical bone volume, albeit with reduced bone mineral density. However, this phenomenon was not observed infemale 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 bonecells were studied in isolation,in vitroosteoclastogenesis was significantly increased in male CD59a-deficientmice, although osteoblast formation was not altered.Our data reveal, for thefirst time, that CD59a is a regulator of bone growth and homeostasis. CD59a ablation inmale mice results in longer and wider bones, but with less density, which is likely a major contributing factorfor their susceptibility to osteoarthritis. Thesefindings increase our understanding of the role of complementregulation in degenerative arthritis.

Item Type: Article
Uncontrolled Keywords: CD59a, Bone, Osteoclast, Ageing, Micro-CT
Depositing User: Symplectic Admin
Date Deposited: 17 Dec 2018 16:46
Last Modified: 16 Sep 2022 07:47
DOI: 10.1016/j.bone.2015.12.014
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3030170