Commercial Bovine Proteoglycan Is Highly Arthritogenic and Can Be Used as an Alternative Antigen Source for PGIA Model

Abstract

Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies.

Metabolomic analysis of biochemical changes in the tissue and urine of proteoglycan-induced spondylitis in mice after treatment with moxibustion

“…Afterward, eight mice were randomly chosen as the healthy control mice (HC group, n = 8) while the other mice were reserved for AS modeling. As previously well described 16 , AS mice models were induced by i.p. injection with an emulsion of 100 μg of cartilage proteoglycans (PG) (Sigma-Aldrich, St. Louis, MO, USA) and 2 mg dimethyldioctadecylammonium (DDA) (Sigma-Aldrich, St. Louis, MO, USA) for 3 times at 21 days intervals .…”

Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis

“…doses of proteoglycan (PG) (50 μ g or 100 μ g) every three days. One week later, experimental arthritis was induced as described by Ishikawa et al, 2014 [ 10 ]. Briefly, mice received three i.p.…”

“…Experimental models induced with some of these antigens, specially collagen and proteoglycan, are being widely employed due to their similarities with the corresponding human disease [ 8 , 9 ]. We recently demonstrated that bovine PG can also induce typical arthritis when associated with dimethyldioctadecylammonium bromide [ 10 ].…”

Vitamin D Deficiency and Rheumatoid Arthritis

“…Twenty-one days after arthritis induction, disease score was evaluated daily until euthanasia. Arthritis severity was assessed as previously described [94], considering a standard visual scoring system based on the degree of edema and erythema ranging from 0 to 4 for each paw. Histopathological analysis, quantification of T cell subsets, and cytokine levels in mice paws were evaluated at the day of euthanasia, i.e., 70 days after arthritis induction.…”