Compromised expression of the complement membrane inhibitor CD59a propagates age-related joint degeneration in mice [Poster Abstract]

Paringe, Vishal, Bloom, A. C., Choy, Ernest Ho Sing ORCID: https://orcid.org/0000-0003-4459-8609, Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676 and Williams, Anwen Sian ORCID: https://orcid.org/0000-0001-6118-020X 2011. Compromised expression of the complement membrane inhibitor CD59a propagates age-related joint degeneration in mice [Poster Abstract]. Arthritis and Rheumatism 63 (s10) , S947-S947. 10.1002/art.33310

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Abstract

Background/Purpose: The influence of complement-mediated innate immune responses on cartilage and bone homeostasis in the ageing joint have not been studied. Inappropriate complement-mediated cell damage is prevented by membrane regulators such as CD59. Synovial tissue expression of CD59 is altered during inflammatory arthritis; elevated CD59 levels may be necessary to protect joint tissues. Roles of CD59 in maintaining tissue equilibrium and structural architecture within the synovial joint have not been described previously. Since CD59a is the primary regulator of membrane attack complex assembly in mice; we used CD59a-gene-deleted mice (CD59a-/-) as tools to unravel the function of CD59a in modulating age-related joint degeneration. Methods: Hind limbs were collected from C57BL/6J wild type (WT) and CD59a-/- mice at 8-, 20- and 50- weeks of age (6 to 10 mice/group). The Mankin score was used to classify the histopathological severity of osteoarthritic (OA) lesions. Three dimensional radiological image analysis provided objective markers of early degenerative changes at the patellofemoral joint and tibiofemoral joint (TFJ). Sulcus angle, coherence angle, TFJ medial and lateral joint space, femoral subchondral bone thickness, lateral femoral and tibial expansion and osteophytes were measured. Statistical analysis by one-way ANOVA unless specified otherwise. C57BL/6J wild type (WT) and CD59a-/- mice. Results: Articular cartilage degeneration was detected earlier in CD59a-/- versus WT. In male mice the Mankin score was 0.1±0.1, 4.2±1.4 (P=0.02; Mann–Whitney U test) and 7.7±1.8 in CD59a-/- compared with 0.2±0.1, 0.9±0.3 and 7.2±1.6 in WT at 8-, 20- and 50- weeks (all mean±SEM). Lateral subluxation occurred earlier and was of significantly greater magnitude in CD59a-/- than WTs (P=0.009; two-way ANOVA). A significant (P=0.03) increase in sulcus angle was noted in CD59a-/- mice over time; no such difference was recorded in WTs. Mean coherence angle measured in CD59a-/- at 8-, 20- and 50- weeks was -6.5, +15.5 and +25 (P=0.0008) compared with -2, -7 and +11 (P=0.01) for WTs indicating significant lateral subluxation of patella with increased age in both strains. TFJ medial and lateral joint space and subchondral bone thickness measurements suggested that bone remodelling was higher in CD59a-/- versus WT at all ages. Osteophytes were clearly visible in CD59a-/- joint specimens across the timecourse but were only observed in WT at 50 weeks. In female mice we observed less articular cartilage pathology than in male mice. However, structural changes indicative of osteoarthritis were consistently more severe in CD59a-/- versus WT mice. Significant joint space narrowing was evident in the medial (P=0.01) and lateral (P=0.01) compartment of the TFJ in CD59a-/- versus WT (two-way ANOVA). Osteophytes were clearly visible in CD59a-/- joint specimens at 20 and 50 weeks but were only observed in WT mice at 50 weeks. Conclusion: CD59a deficiency markedly accelerates the progression of age-related joint degeneration in mice. The identification of disease-modifying markers is necessary in order to improve the prediction of disease progression at the individual level and open exciting possibilities for novel treatment options for OA.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine
Additional Information:	Abstracts of the American College of Rheumatology & Association of Rheumatology Health Professionals, Annual Scientific Meeting, November 4–9, 2011 Chicago, Illinois
Publisher:	Wiley-Blackwell
ISSN:	0004-3591
Last Modified:	09 Aug 2024 13:53
URI:	https://orca.cardiff.ac.uk/id/eprint/43502

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