Rodent Preclinical Models for Developing Novel Antiarthritic Molecules: Comparative Biology and Preferred Methods for Evaluating Efficacy

Bolon, Brad; Stolina, Marina; King, Caroline; Middleton, Scot; Gasser, J; Zack, Debra; Feige, Ulrich

doi:10.1155/2011/569068

Cited by 99 publications

(126 citation statements)

References 148 publications

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“…Paws selected for histology are fixed in formalin, decalcified, and processed to sagittal hemisections representing larger (eg, tarsal, carpal) as well as smaller digital joints. 3 Some investigators prefer to embed the hind paws in the sagittal plane, whereas forepaws are oriented horizontally. In addition to the usual considerations for histology, particular attention should be given to sample preparation.…”

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confidence: 99%

Mouse Models of Rheumatoid Arthritis

Caplazi¹,

Baca²,

Barck³

et al. 2015

Vet Pathol

117

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Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody-induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFD ARE mouse, in which arthritis results from overexpression of TNF-a, a master proinflammatory cytokine that drives disease in many patients.

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confidence: 99%

Mouse Models of Rheumatoid Arthritis

Caplazi¹,

Baca²,

Barck³

et al. 2015

Vet Pathol

117

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“…16 These models have proven to predict the responsiveness of human RA patients. Structural and immunological changes in CIA best resemble RA, while AIA lesions are most severe and consistent.…”

Section: Discussionmentioning

confidence: 99%

“…The widespread formation of osteophytes along the periosteal surface may eventually result in fusion (ankylosis) of the affected joints with joint deformities resulting in a significant reduction of mobility. 16 Hence, the study duration was restricted to 3 weeks to include the acute and chronic phases of rat CIA. Symptomatic rats received analgesic treatment.…”

Section: Animal Modelmentioning

confidence: 99%

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In vivotherapy monitoring of experimental rheumatoid arthritis in rats using near-infrared fluorescence imaging

et al. 2014

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Abstract. An in vivo near-infrared fluorescence (NIRF) imaging technique is described for therapy monitoring of ankle joints affected by collagen-induced arthritis, a model of human rheumatoid arthritis. Arthritis was induced in rats by intradermal injections of collagen and Freund's incomplete adjuvant. For in vivo imaging, the nonspecific NIR dye tetrasulfocyanine (TSC) was used. Prior to and after treatment with a nonsteroidal anti-inflammatory drug, meloxicam, or analgesic drug, tramadol hydrochloride (which served as no-therapy control), normalized fluorescence intensities of each ankle joint were measured. Additionally, each ankle joint was characterized by clinical arthritis scoring and histopathology. Over a 3-week treatment period, a significant difference in disease progression between animals treated with meloxicam and tramadol hydrochloride was detected. A statistically significant improvement in ankle joint pathology from high-or moderate-grade to moderate-or low-grade upon meloxicam therapy, as determined by clinical evaluation, translated into a significant decrease in fluorescence intensity. In contrast, all arthritic joints of the no-therapy control group deteriorated to high-grade arthritis with high-fluorescence intensities in NIRF imaging. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…1, with these exceptions: CCL2, chemokine (C-C motif) ligand 2 (formerly MCP-1); chemokine (C-X-C motif) ligand 1 (formerly KC/GRO); RANKL, receptor activator of nuclear factor-B. Gross images reprinted from (Bolon et al 2011), while the cytokine signatures were reported in (Stolina et al 2008(Stolina et al , 2009 patients with comparable conditions. Human patients with RA have similar clinical and pathological presentations, but the AIDx is nonetheless a heterogeneous condition in which some patients respond only to interleukin (IL)-1 inhibition, others improve with tumor necrosis factor-a (TNF-a) blockade, still others recover following anti-IL-6 therapy, and some are not helped by quenching any of these ''master'' cytokines (Fitzgerald et al 2005;Senolt et al 2009;Patel and Moreland 2010;Turkstra, Ng, and Schuffham 2011).…”

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confidence: 99%

Cellular and Molecular Mechanisms of Autoimmune Disease

Bolon

2011

Toxicol Pathol

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Autoimmune disease (AIDx) results from failure to sustain tolerance to self molecules. Dozens of AIDx involving one or multiple organ systems afflict 3% or more of people worldwide (>75% women). Predisposing factors for AIDx include genetic background, hormonal status, pathogens, and xenobiotic exposures. The incidence of AIDx is higher in individuals living in developed nations, including recent immigrants. Patients may have several AIDx simultaneously. Certain AIDx can prevent other AIDx. A history of AIDx raises the risk for developing hematopoietic neoplasia. Some common mechanisms for losing self-tolerance include reduced deletion or enhanced activation of autoreactive CD4 þ T-helper (Th) lymphocytes, defective immunomodulation by CD4 þ regulatory (Treg) and CD8 þ suppressor (Ts) T-lymphocytes, dysregulated signaling (leading to a relative increase in pro-inflammatory cytokines), comparable structure between self-antigens and foreign molecules, or expression of new epitopes on previously hidden or xenobiotic-modified self proteins. Organ-specific AIDx is generally a cell-mediated (Th1 or Th17) process, while multi-organ AIDx also incorporates a robust autoantibody (Th2) component. Cytokine signatures of different AIDx overlap incompletely; for a given AIDx, different patients have divergent cytokine profiles. Newer anti-AIDx agents are based on our increasing knowledge of AIDx pathogenesis and usually attempt to reverse lymphocyte dysfunction, quell pro-inflammatory signaling, or restore self-tolerance.

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Rodent Preclinical Models for Developing Novel Antiarthritic Molecules: Comparative Biology and Preferred Methods for Evaluating Efficacy

Cited by 99 publications

References 148 publications

Mouse Models of Rheumatoid Arthritis

Mouse Models of Rheumatoid Arthritis

In vivotherapy monitoring of experimental rheumatoid arthritis in rats using near-infrared fluorescence imaging

Cellular and Molecular Mechanisms of Autoimmune Disease

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