Arthritis Models
Inflammatory Joint Disease Models
Pharmacology & Efficacy Studies for Rheumatoid Arthritis
Rodent models of immune-mediated arthritis (RMIA) are commonly used to evaluate the mechanisms of inflammatory joint disease, as well as test the efficacy of anti-arthritic compounds. Collagen induced arthritis (CIA) and adjuvant induced arthritis (AIA) are two commonly used models for this purpose. At MLM, we offer our clients the novel and rapid collagen antibody-induced arthritis (CAIA) model as well.
Our expertise includes:
- Adjuvant-induced RA (AIA)
- Collagen antibody-induced RA (CAIA)
- Collagen-induced RA (CIA)
See below information to learn more about our experience/readouts options:
Experience | Readouts | Options |
---|---|---|
Biologics | Arthritis score | Biomarkers (protein, mRNA) |
NCEs | Paw thickness | Cell populations by FACS |
Plant-based compounds | Body Weights | Histology/IHC |
siRNA | PK | |
Adjuvant-Induced Arthritis (AIA) Model
Extensively Utilized Model for Arthritis Studies
Species available: rat AIA, pig AIA
Complete Freund's adjuvant is used to initiate induction of arthritis. This model was the original model of RA, has been extensively used to preclinical screening of new anti-arthritis compounds and has successfully predicted activity and toxicity in multiple new therapeutics. After a single injection of the adjuvant, a rapid, reliable, robust and easily measureable polyarthritis develops. The joint pathology seen in AIA share the cartilage degradation, bone reportion and cellular influx seen in human RA. This model is also T cell and neutrophil dependant with no requirement for B cells. Cytokines of both the Th1 and Th17 phenotype (eg. IL-1, IL-6, IL-17A, IL-21) are believed to play a role in the joint pathology. As this model is generally less severe than the CIA and is transient (normally resolving after a month), lower doses of test compounds can be effective in this model. The pathology however is not limited to the extremeties as the spine, GI tract, skin and even the eyes can be affected.
The injection of CFA in the tail base results in a chronic arthritis involving multiple joints, promoting a widespread systemic disease that results in severe discomfort and distress. By administering the CFA intrarticular and periarticular into the joint, you achieve a less servere monoarthritis within a few days.
Study Details
- Type: Monoarthritis or Polyarthritis
- Length: 10-28 days
- Dosing Paradigms: Prophylactic or Therapeutic
- Dosing routes: PO, IP, SC, IV, Infusion pump
- Controls: Dexamethasone, Enbrel, Morphine
- Assessments: Arthritis Score, Hind paw thickness, Body weight
Optional Assessments:
- Circulating or tissue level Biomarker analysis (protein or mRNA)
- Histological/IHC assessment of joints
- PK blood collections
Collagen Antibody-Induced Arthritis (CAIA) Model
Rapid, Synchronized Arthritis Induction Bypassing Humoral Response
Species available: Mouse CAIA
The Collagen Antibody-Induced Arthritis (CAIA) model is a rapid and synchronized alternative to the Collagen-Induced Arthritis (CIA) model. A cocktail of arthritogenic monoclonal antibodies to Collagen-II, combined with a immunogenic boost of LPS, rapidly induces arthritis in Balb/c mice. These arthritis-inducing antibodies recognize a wide range of epitopes on the Collagen-II molecule and thereby allow formation of large immune complexes within cartilage. Because these anti-collagen targeting antibodies are administered directly, the CAIA model bypasses the need for development of a humoral response against collagen involving T and B cell interactions. This allows for a far more rapid induction of disease, with onset occuring within 48 hours of the LPS boost and a total study duration of as little as 10 days.
CAIA Study Details:
- Length: 10-18 days
- Dosing Paradigms: Prophylactic (developing or semi-established)
- Dosing routes: PO, IP, SC, IV, Infusion pump
- Controls: Dexamethasone, Enbrel
- Assessments: Arthritis Score, Hind paw thickness, Body weight
Optional Assessments:
- Circulating or tissue level Biomarker analysis (protein or mRNA)
- Histological/IHC assessment of joints
- PK blood collections
- Cell populations in the spleen/lymph node by FACS
Collagen Induced Arthritis (CIA) Model
Validated Model for RA/OA Studies
Species available: Mouse CIA, Rat CIA
The Collagen Induced Arthritis (CIA) model is a commonly used model as it shares immunological and pathological similarities to human RA. Arthritis is initiated by intradermal injections of Collagen Type II (CII) emulsified in Complete Freund's Adjuvant (CFA). This causes an immune response generating antibodies to CII. Therefore there is both a T cell and B cell component to the pathology. The joint destruction in collagen-induced arthritis involves cartilage destruction, bone resporption, synovial hyperplasia and periarticular cell infiltration thereby sharing many similarities to human RA.
CIA Study Details:
- Length: 35-42 days
- Dosing Paradigms: Prophylactic (developing or semi-established), Therapeutic
- Dosing routes: PO, IP, SC, IV, Infusion pump
- Controls: Dexamethasone
- Assessments: Arthritis Score, Hind paw thickness, Body weight
Optional Assessments:
- Circulating or tissue level Biomarker analysis (protein or mRNA)
- Collagen antibody levels
- Cell Populations in Spleen/Lymph Node by FACS
- Histological/IHC assessment of joints
- PK blood collections
Longitudinal Section of the PAW from CIA Mice Model (H&E Staining)