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Open Access 01-08-2010 | Research article

Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis

Authors: Sindhu T Mohanty, Lucksy Kottam, Alessandra Gambardella, Martin J Nicklin, Les Coulton, David Hughes, Anthony G Wilson, Peter I Croucher, Ilaria Bellantuono

Published in: Arthritis Research & Therapy | Issue 4/2010

Abstract

Introduction

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily involving the synovium. Evidence in recent years has suggested that the bone marrow (BM) may be involved, and may even be the initiating site of the disease. Abnormalities in haemopoietic stem cells' (HSC) survival, proliferation and aging have been described in patients affected by RA and ascribed to abnormal support by the BM microenvironment. Mesenchymal stem cells (MSC) and their progeny constitute important components of the BM niche. In this study we test the hypothesis that the onset of inflammatory arthritis is associated with altered self-renewal and differentiation of bone marrow MSC, which alters the composition of the BM microenvironment.

Methods

We have used Balb/C Interleukin-1 receptor antagonist knock-out mice, which spontaneously develop RA-like disease in 100% of mice by 20 weeks of age to determine the number of mesenchymal progenitors and their differentiated progeny before, at the start and with progression of the disease.

Results

We showed a decrease in the number of mesenchymal progenitors with adipogenic potential and decreased bone marrow adipogenesis before disease onset. This is associated with a decrease in osteoclastogenesis. Moreover, at the onset of disease a significant increase in all mesenchymal progenitors is observed together with a block in their differentiation to osteoblasts. This is associated with accelerated bone loss.

Conclusions

Significant changes occur in the BM niche with the establishment and progression of RA-like disease. Those changes may be responsible for aspects of the disease, including the advance of osteoporosis. An understanding of the molecular mechanisms leading to those changes may lead to new strategies for therapeutic intervention.

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Title: Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis
Authors: Sindhu T Mohanty
Lucksy Kottam
Alessandra Gambardella
Martin J Nicklin
Les Coulton
David Hughes
Anthony G Wilson
Peter I Croucher
Ilaria Bellantuono
Publication date: 01-08-2010
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 4/2010
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar3098

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Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis

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Results

Conclusions

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