title: Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice.
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.
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Anja C
authors.initials: AC
authors.lastname: Bloom
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Fraser L
authors.initials: FL
authors.lastname: Collins
authors.affiliation: Bone Research Group, Institute of Ageing & Chronic Disease, University ofLiverpool, Liverpool, UK.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Van't Hof
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Ryan
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Jones
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, University of Göteborg, Gothenburg, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Erlandsson
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, University of Göteborg, Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bokarewa
authors.affiliation: Matrix Biology and Tissue Repair, Dental School, Cardiff University, Cardiff, UK; Arthritis Research UK Centre for Biomechanics and Bioengineering, Cardiff University, Cardiff, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aeschlimann
authors.affiliation: Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK; Arthritis Research UK Centre for Biomechanics and Bioengineering, Cardiff University, Cardiff, UK.
authors.forename: Bronwen A J
authors.initials: BAJ
authors.lastname: Evans
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK; Arthritis Research UK Centre for Biomechanics and Bioengineering, Cardiff University, Cardiff, UK. Electronic address: williamsas@cf.ac.uk.
authors.forename: Anwen S
authors.initials: AS
authors.lastname: Williams
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001846:Bone Development; D001854:Bone Marrow Cells / Q000473:pathology; D016723:Bone Remodeling; D001842:Bone and Bones / Q000473:pathology*; D018957:CD59 Antigens / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D008297:Male; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012727:Sex Characteristics
chemical_list: D018957:CD59 Antigens; C539311:CD59a protein, mouse; D003165:Complement System Proteins
keywords: Ageing; Bone; CD59a; Micro-CT; Osteoclast