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.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Mohanty ST,Kottam L,Gambardella A,Nicklin MJ,Coulton L,Hughes D,Wilson AG,Croucher PI,Bellantuono Idoi
10.1186/ar3098subject
Has Abstractpub_date
2010-01-01 00:00:00pages
R149issue
4eissn
1478-6354issn
1478-6362pii
ar3098journal_volume
12pub_type
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journal_title:Arthritis research & therapy
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pub_type: 杂志文章,已发布勘误
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journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
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journal_title:Arthritis research & therapy
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Arthritis research & therapy
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