Assessment of collagen antibody-induced arthritis in BALB/c mice using bioimaging analysis and histopathological examination

Abstract

The aim of this study was to examine the therapeutic potential of sulfasalazine and prednisolone in a mouse collagen antibody-induced arthritis (CAIA) model. Twenty-five male BALB/c mice were randomly divided into five groups: group 1 (G1): control, group 2 (G2): probe control, group 3 (G3): CAIA, group 4 (G4): CAIA+sulfasalazine (10 mg/kg, oral), and group 5 (G5): CAIA+prednisolone (100 mg/kg, oral). Fluorescence bioimaging was performed in vivo 24 and 48 h after treatment with a fluorescence probe (OsteoSense® 680 EX), and all mice were sacrificed. The hind knee joints were fixed in 10% neutral phosphate-buffered formalin, and micro-computed tomography (micro-CT) and histopathological analyses were performed. The paw thickness increased in a time-dependent manner in G3 mice, but trended toward a decrease in both G4 and G5 mice. Fluorescence intensity increased in G3 mice at 24 and 48 h after fluorescence probe treatment, but the fluorescence intensity in G4 and G5 mice was lower than that in G3. Micro-CT analyses showed that the joint surfaces of G3 mice had a rough and irregular articular appearance, but the occurrence of these irregularities was lower in G4 and G5. Hematoxylin and eosin and Safranin O-fast green staining confirmed that destruction of the cartilage and bony structures, synovial hyperplasia, and inflammatory cell infiltration all occurred in G3, and that the occurrence of these phenomena was lower in G4 and G5 than in G3. Taken together, these results suggest that sulfasalazine and prednisolone can reduce acute rheumatoid arthritis in mice.

Kava‐241 reduced periodontal destruction in a collagen antibody primed Porphyromonas gingivalis model of periodontitis

“…The magnitude of the periodontal destruction allowed a significant effect size amenable for the evaluation of novel anti‐inflammatory therapeutics with minimal risk of complications such as increased period of disease induction or increased risk of mouse death that may occur in case of surgical approach or repeated anaesthesia. AB is a well‐described method to induce arthritis in mice (Sim, Lee, Lee, & Kang, ; Tang & Amar, ). Rheumatoid arthritis and periodontitis shared several aetiopathogenic mechanisms related to the immune host response and to cytokines secretion (Culshaw, McInnes, & Liew, ).…”

Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice

“…Because most common arthritis models do not develop in old, skeletally mature animals, there is no alternate erosive arthritis model available to avoid this effect. Consistently, the use of an alternative method such as optical imaging with a hydroxyapatite‐targeting fluorescent marker (OsteoProbe) also showed limited sensitivity to quantify bone damage . Advances in identifying differences between physiological and pathophysiological bone remodeling are necessary for the development of novel pathology‐associated bone tracers.…”

“…Consistently, the use of an alternative method such as optical imaging with a hydroxyapatite-targeting fluorescent marker (OsteoProbe) also showed limited sensitivity to quantify bone damage. (41) Advances in identifying differences between physiological and pathophysiological bone remodeling are necessary for the development of novel pathologyassociated bone tracers. Overall, our study demonstrates that [ 18 F]fluoride is not an appropriate tracer to quantify the extent of local inflammation-mediated bone damage and remodeling processes in joints from this TNF-driven arthritis model.…”

Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues

“…At the effector level of arthritis, apart from targeting effector molecules, like C5 [ 67 , 153 ] and its break down product C5a [ 65 , 154 , 155 ], receptors (FcRs [ 156 ], TLRs [ 157 ]), transcription factors [ 158 , 159 ]), and cytokines, using different strategies and drugs [ 160 , 161 , 162 ], methods for direct targeting of pathogenic IgG antibodies could be attractive and optimal for therapeutic applications.…”