The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

Teixeira, José H.; Silva, Andreia M.; Almeida, Maria Inês; Bessa-Gonçalves, Mafalda; Cunha, Carla; Barbosa, Mário A.; Santos, Susana G.

doi:10.3390/ijms20215436

Open AccessArticle

The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

by

José H. Teixeira

^1,2

,

Andreia M. Silva

^1,2,

Maria Inês Almeida

¹

,

Mafalda Bessa-Gonçalves

^1,2

,

Carla Cunha

¹

,

Mário A. Barbosa

^1,2 and

Susana G. Santos

^1,2,*

¹

i3S—Instituto de Investigação e Inovação em Saúde and INEB—Instituto Nacional de Engenharia Biomédica, University of Porto, 4200-135 Porto, Portugal

²

Department of Molecular Biology, ICBAS—Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2019, 20(21), 5436; https://doi.org/10.3390/ijms20215436

Submission received: 20 September 2019 / Revised: 29 October 2019 / Accepted: 29 October 2019 / Published: 31 October 2019

(This article belongs to the Special Issue Research of Pathogenesis and Novel Therapeutics in Arthritis 2.0)

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Abstract

Rheumatoid arthritis (RA) is a systemic disease that affects the osteoarticular system, associated with bone fragility and increased risk of fractures. Herein, we aimed to characterize the systemic impact of the rat collagen-induced arthritis (CIA) model and explore its combination with femoral bone defect (FD). The impact of CIA on endogenous mesenchymal stem/stromal cells (MSC) was also investigated. CIA induction led to enlarged, more proliferative, spleen and draining lymph nodes, with altered proportion of lymphoid populations. Upon FD, CIA animals increased the systemic myeloid cell proportions, and their expression of co-stimulatory molecules CD40 and CD86. Screening plasma cytokine/chemokine levels showed increased tumor necrosis factor-α (TNF-α), Interleukin (IL)-17, IL-4, IL-5, and IL-12 in CIA, and IL-2 and IL-6 increased in CIA and CIA+FD, while Fractalkine and Leptin were decreased in both groups. CIA-derived MSC showed lower metabolic activity and proliferation, and significantly increased osteogenic and chondrogenic differentiation markers. Exposure of control-MSC to TNF-α partially mimicked the CIA-MSC phenotype in vitro. In conclusion, inflammatory conditions of CIA led to alterations in systemic immune cell proportions, circulating mediators, and in endogenous MSC. CIA animals respond to FD, and the combined model can be used to study the mechanisms of bone repair in inflammatory conditions.

Keywords: rheumatoid arthritis; collagen-induced arthritis; microenvironment; inflammation; mesenchymal stem/stromal cells; bone injury; repair/regeneration

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MDPI and ACS Style

Teixeira, J.H.; Silva, A.M.; Almeida, M.I.; Bessa-Gonçalves, M.; Cunha, C.; Barbosa, M.A.; Santos, S.G. The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions. Int. J. Mol. Sci. 2019, 20, 5436. https://doi.org/10.3390/ijms20215436

AMA Style

Teixeira JH, Silva AM, Almeida MI, Bessa-Gonçalves M, Cunha C, Barbosa MA, Santos SG. The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions. International Journal of Molecular Sciences. 2019; 20(21):5436. https://doi.org/10.3390/ijms20215436

Chicago/Turabian Style

Teixeira, José H., Andreia M. Silva, Maria Inês Almeida, Mafalda Bessa-Gonçalves, Carla Cunha, Mário A. Barbosa, and Susana G. Santos. 2019. "The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions" International Journal of Molecular Sciences 20, no. 21: 5436. https://doi.org/10.3390/ijms20215436

APA Style

Teixeira, J. H., Silva, A. M., Almeida, M. I., Bessa-Gonçalves, M., Cunha, C., Barbosa, M. A., & Santos, S. G. (2019). The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions. International Journal of Molecular Sciences, 20(21), 5436. https://doi.org/10.3390/ijms20215436

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The Systemic Immune Response to Collagen-Induced Arthritis and the Impact of Bone Injury in Inflammatory Conditions

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