In Vivo Models for Inflammatory Arthritis

Jones, Gareth Wyn; Hill, David; Sime, Katie; Williams, Anwen Siân

doi:10.1007/978-1-4939-7568-6_9

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…of MSCs from wild type and Sdc3 −/− mice were tested in the AIA mouse model of inflammatory arthritis. This model shares many histopathological and clinical features seen in human RA 31 . MSC treatments (wild type and Sdc3 −/− ) reduced joint swelling as a measure of joint inflammation compared to serum-free medium control at days 2 (p < 0.05) and 3 (p < 0.05) post arthritis induction (Fig.…”

Section: Syndecan-3 Loss In Mscs Improves Arthritic Symptoms In Aia mentioning

confidence: 83%

Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo

Jones¹,

Stefan²,

Kay³

et al. 2020

Sci Rep

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Rheumatoid arthritis (RA) is a debilitating and painful inflammatory autoimmune disease characterised by the accumulation of leukocytes in the synovium, cartilage destruction and bone erosion. The immunomodulatory effects of bone marrow derived mesenchymal stem cells (MSCs) has been widely studied and the recent observations that syndecan-3 (SDC3) is selectively pro-inflammatory in the joint led us to hypothesise that SDC3 might play an important role in MSC biology. MSCs isolated from bone marrow of wild type and Sdc3−/− mice were used to assess immunophenotype, differentiation, adhesion and migration properties and cell signalling pathways. While both cell types show similar differentiation potential and forward scatter values, the cell complexity in wild type MSCs was significantly higher than in Sdc3−/− cells and was accompanied by lower spread surface area. Moreover, Sdc3−/− MSCs adhered more rapidly to collagen type I and showed a dramatic increase in AKT phosphorylation, accompanied by a decrease in ERK1/2 phosphorylation compared with control cells. In a mouse model of antigen-induced inflammatory arthritis, intraarticular injection of Sdc3−/− MSCs yielded enhanced efficacy compared to injection of wild type MSCs. In conclusion, our data suggest that syndecan-3 regulates MSC adhesion and efficacy in inflammatory arthritis, likely via induction of the AKT pathway.

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Section: Syndecan-3 Loss In Mscs Improves Arthritic Symptoms In Aia mentioning

confidence: 83%

Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo

Jones¹,

Stefan²,

Kay³

et al. 2020

Sci Rep

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show abstract

“…Collagen-induced arthritis (CIA) is one of the most widely accepted murine models for human RA. The DBA/1 strain of mice used in this model is uniquely susceptible to developing RA in response to immunization with type II collagen (CII) plus complete Freund’s adjuvant (CFA) [101,102,103,104]. Interestingly, these mice are also susceptibility to dyslipidemia when on an atherogenic diet () [105,106].…”

Section: Microbial Dysbiosis and Tmao Promote Rheumatoid Arthritismentioning

confidence: 99%

The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis

et al. 2019

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Diet and microbiota each have a direct impact on many chronic, inflammatory, and metabolic diseases. As the field develops, a new perspective is emerging. The effects of diet may depend on the microbiota composition of the intestine. A diet that is rich in choline, red meat, dairy, or egg may promote the growth, or change the composition, of microbial species. The microbiota, in turn, may produce metabolites that increase the risk of cardiovascular disease. This article reviews our current understanding of the effects of the molecule trimethylamine-N-oxide (TMAO) obtained from food or produced by the microbiota. We review the mechanisms of actions of TMAO, and studies that associate it with cardiovascular and chronic kidney diseases. We introduce a novel concept: TMAO is one among a group of selective uremic toxins that may rise to high levels in the circulation or accumulate in various organs. Based on this information, we evaluate how TMAO may harm, by exacerbating inflammation, or may protect, by attenuating amyloid formation, in autoimmune diseases such as rheumatoid arthritis.

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“…The anti-inflammatory capability of MSCs from wild type and Sdc3 −/− mice were tested in the AIA mouse model of inflammatory arthritis. This model shares many histopathological and clinical features seen in human RA 31 . MSC treatments (wild type and Sdc3 −/− ) reduced joint swelling as a measure of joint inflammation compared to serum-free medium control at days 2 (p<0.05) and 3 (p<0.05) post arthritis induction (Fig.…”

Section: Resultsmentioning

confidence: 83%

MSCs from syndecan-3 null mice exhibit enhanced adhesion to collagen type I, hyperactivation of the AKT pathway and increased efficacy in inflammatory arthritis

Jones

Stefan

Kay

et al. 2020

Preprint

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1AbstractRheumatoid arthritis (RA) is a debilitating and painful inflammatory autoimmune disease characterised by the accumulation of leukocytes in the synovium, cartilage destruction and bone erosion. The immunomodulatory effects of bone marrow derived mesenchymal stem cells (MSCs) has been widely studied and the recent observations that syndecan-3 (SDC3) is selectively pro-inflammatory in the joint led us to hypothesise that SDC3 might play an important role in MSC biology. MSCs isolated from bone marrow of wild type and Sdc3−/− mice were used to assess immunophenotype, differentiation, adhesion and migration properties and cell signalling pathways. While both cell types show similar differentiation potential and forward scatter values, the cell complexity in wild type MSCs was significantly higher than in Sdc3−/− cells and was accompanied by lower spread surface area. Moreover, Sdc3−/− MSCs adhered more rapidly to collagen type I and showed a dramatic increase in AKT phosphorylation, accompanied by a decrease in ERK1/2 phosphorylation compared with control cells. In a mouse model of antigen-induced inflammatory arthritis, intraarticular injection of Sdc3−/− MSCs yielded enhanced recovery compared to injection of wild type MSCs. In conclusion, our data suggest that syndecan-3 regulates MSC adhesion and efficacy in inflammatory arthritis, likely via induction of the AKT pathway.

show abstract

In Vivo Models for Inflammatory Arthritis

Cited by 15 publications

References 32 publications

Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo

Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo

The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis

MSCs from syndecan-3 null mice exhibit enhanced adhesion to collagen type I, hyperactivation of the AKT pathway and increased efficacy in inflammatory arthritis

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