Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Syndesmophyte Formation Is Associated with Low-Grade Spine Inflammation and Disconnected From Peripheral Arthritis in Mice Immunized with Recombinant Human Aggrecan G1 Domain.
Ramez, Mohamed, Forde, Toni S., Kudryavtseva, Elena, Adarichev, Vyacheslav A.
The balance between inflammation-driven cartilage and bone erosion and new bone formation is set at different levels in rheumatoid arthritis and ankylosing spondylitis. Inflammation and tissue damage usually prepare the stage for the later repair process of new tissue formation like syndesmophytes and bone fusions in AS. To understand mechanisms of bone remodeling in inflammatory conditions, we developed a murine model of spondylitis induced with aggrecan immunizations.
Human aggrecan G1 domain (1235 aa of ACAN-201) tagged with 6xHis was cloned using a baculovirus system, and the fusion protein was overexpressed in insect cells. Secreted rhAG1 protein was isolated using Ni-NTA resin. Protein identity and purity was characterized with SDS-PAGE and immunodetection. BALB/c females were immunized intraperitoneally with rhAG1 emulsified either in Complete Freund's adjuvant (CFA) or in dimethyldioctadecylammonium bromide (DDA) adjuvant or DDA alone. Mice were scored for visual signs of peripheral arthritis. Histopathology sections of paws and thoracic-caudal spines were stained with hematoxylin & eosin and alcian blue and examined for inflammation and intervertebral disk (IVD) afflictions.
Mice immunized with rhAG1-DDA showed slightly higher arthritis severity than rhAG1-CFA group. Slowly progressive arthritis reached maximum after four immunizations. Histopathological examination of paw sections confirmed the presence of inflammatory cells, but severity of arthritis was rather mild. Despite the slow peripheral inflammation, histopathological assessment of spine sections revealed massive ventral chondroplasia of fibrocartilaginous annulus fibrosus-like cells that had been displacing anterior longitudinal ligament. Ventral aspects of enthesis, annulus fibrosus, and growth plate were mainly affected. Chondrophyte/syndesmophyte sizes reached up to 50% of the size of IVD. One to three syndesmophytes per every spine were observed in 20% of examined mice. The most affected regions were the junction of sacrum with lumbar and caudal parts of axial skeleton: S1-L6 and S4-Ca1. We observed consistent but low grade inflammation around afflicted skeletal regions that strongly correlated with spine chondrophytosis, r=0.81. Correlation between peripheral joints inflammation and syndesmophyte formation was much weaker, r=0.29.
A new murine model for syndesmophyte formation with disconnect between otherwise weak peripheral joints inflammation is developed. The balance between peripheral inflammation, spondylitis and chondrophytosis seems to be dependent on the source, biochemical properties and immunogenicity of the immunizing aggrecan antigen.
To cite this abstract, please use the following information:
Ramez, Mohamed, Forde, Toni S., Kudryavtseva, Elena, Adarichev, Vyacheslav A.; Syndesmophyte Formation Is Associated with Low-Grade Spine Inflammation and Disconnected From Peripheral Arthritis in Mice Immunized with Recombinant Human Aggrecan G1 Domain. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1348