Abstract:
INTRODUCTION:Osteoclastogenesis plays an important role in the bone erosion of rheumatoid arthritis (RA). Recently, Notch receptors have been implicated in the development of osteoclasts. However, the responsible Notch ligands have not been identified yet. This study was undertaken to determine the role of individual Notch receptors and ligands in osteoclastogenesis. METHODS:Mouse bone marrow-derived macrophages or human peripheral blood monocytes were used as osteoclast precursors and cultured with receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) to induce osteoclasts. Osteoclasts were detected by tartrate-resistant acid phosphatase (TRAP) staining. K/BxN serum-induced arthritic mice and ovariectomized mice were treated with anti-mouse Delta-like 1 (Dll1) blocking monoclonal antibody (mAb). RESULTS:Blockade of a Notch ligand Dll1 with mAb inhibited osteoclastogenesis and, conversely, immobilized Dll1-Fc fusion protein enhanced it in both mice and humans. In contrast, blockade of a Notch ligand Jagged1 enhanced osteoclastogenesis and immobilized Jagged1-Fc suppressed it. Enhancement of osteoclastogenesis by agonistic anti-Notch2 mAb suggested that Dll1 promoted osteoclastogenesis via Notch2, while suppression by agonistic anti-Notch1 mAb suggested that Jagged1 suppressed osteoclastogenesis via Notch1. Inhibition of Notch signaling by a gamma-secretase inhibitor suppressed osteoclastogenesis, implying that Notch2/Dll1-mediated enhancement was dominant. Actually, blockade of Dll1 ameliorated arthritis induced by K/BxN serum transfer, reduced the number of osteoclasts in the affected joints and suppressed ovariectomy-induced bone loss. CONCLUSIONS:The differential regulation of osteoclastogenesis by Notch2/Dll1 and Notch1/Jagged1 axes may be a novel target for amelioration of bone erosion in RA patients.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Sekine C,Koyanagi A,Koyama N,Hozumi K,Chiba S,Yagita Hdoi
10.1186/ar3758subject
Has Abstractpub_date
2012-03-05 00:00:00pages
R45issue
2eissn
1478-6354issn
1478-6362pii
ar3758journal_volume
14pub_type
杂志文章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 ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3098
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1677-x
更新日期:2018-08-16 00:00:00
abstract:BACKGROUND:The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA). METHODS:This was a non-randomised, single-centre, pro...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13075-017-1244-x
更新日期:2017-02-10 00:00:00
abstract:INTRODUCTION:During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful. Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common. Endocannabinoids have the...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0437-9
更新日期:2014-09-27 00:00:00
abstract:BACKGROUND:Rheumatoid arthritis (RA) is often characterized by the presence of rheumatoid factor, anti-citrullinated protein antibodies, and bone erosions. Current therapies can compromise immunity, leading to risk of infection. The interleukin-20 receptor (IL-20R) axis comprising IL-19, IL-20, and IL-24 and their shar...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-016-0964-7
更新日期:2016-03-11 00:00:00
abstract:INTRODUCTION:The aim of the study was to determine whether Olf1/EBF associated zinc finger protein (OAZ), a transcription factor encoded by a positional systemic lupus erythematosus (SLE) candidate gene, plays a functional role in the pathogenesis in SLE. METHODS:Gene expression levels in peripheral blood cells (PBLs)...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2972
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:In cross-sectional studies, patients with rheumatoid arthritis (RA) have higher coronary artery calcium (CAC) than controls. However, their rate of progression of CAC and the predictors of CAC progression have heretofore remained unknown. METHODS:Incidence and progression of CAC were compared in 155 patie...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4314
更新日期:2013-09-25 00:00:00
abstract::The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. The cells were isolated from human articular cartilage obtained at surgery and were cultured in the absence or presence of ET-1 with or without inhibi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1489
更新日期:2005-01-01 00:00:00
abstract::B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have expanded our understanding of effector functions of B cells as well as their roles in human autoimmune diseases. The current review addresses the role of c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2780
更新日期:2009-01-01 00:00:00
abstract::Ankylosing spondylitis and axial spondyloarthropathy have characteristic age- and sex-specific onset patterns, typical entheseal lesions, and marked heritability, but the integrative mechanisms causing the pathophysiological and structural alterations remain largely undefined. Myofascial tissues are integrated in the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4532
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is a rare disease with studies limited by small sample sizes. Electronic health records (EHRs) represent a powerful tool to study patients with rare diseases such as SSc, but validated methods are needed. We developed and validated EHR-based algorithms that incorporate billing codes ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2092-7
更新日期:2019-12-30 00:00:00
abstract:BACKGROUND:The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor κB ligand (RANKL) blockade on severity of arthritis, bone destruction, an...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0931-3
更新日期:2016-01-23 00:00:00
abstract:INTRODUCTION:Mesenchymal stem cells (MSCs) represent promising applications in rheumatoid arthritis (RA). However, the inflammatory niche in the RA synovium could adversely affect MSC function. This study was designed to investigate biologic and immunologic properties of synovium-derived MSCs (SMSCs) in RA, with partic...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4355
更新日期:2013-10-29 00:00:00
abstract:INTRODUCTION:Progression of joint destruction in rheumatoid arthritis (RA) is partly heritably; 45 to 58% of the variance in joint destruction is estimated to be explained by genetic factors. The binding of RANKL (Receptor Activator for Nuclear Factor κ B Ligand) to RANK results in the activation of TRAF6 (tumor necros...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4558
更新日期:2014-05-07 00:00:00
abstract:INTRODUCTION:The high-affinity receptor for IgG Fcgamma/CD64 is critical for the development of lupus nephritis (LN). Cross-linking Fc receptor on recruited monocytes by IgG-containing immune complexes is a key step in immune-complex-mediated nephritis in systemic lupus erythematosus (SLE). The goal of this study was t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2590
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:We sought to assess vascularity in wrist tenosynovitis by using power Doppler ultrasound (PDUS) and to compare detection of intra- and peritendinous vascularity with that of contrast-enhanced grey-scale ultrasound (CEUS). METHODS:Twenty-six tendons of 24 patients (nine men, 15 women; mean age ± SD, 54.4 ±...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3185
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1208-6
更新日期:2017-01-13 00:00:00
abstract:BACKGROUND:African Americans with systemic lupus erythematosus (SLE) have increased renal disease compared to Caucasians, but differences in other comorbidities have not been well-described. We used an electronic health record (EHR) technique to test for differences in comorbidities in African Americans compared to Cau...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1561-8
更新日期:2018-04-10 00:00:00
abstract:INTRODUCTION:Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0632-3
更新日期:2015-05-21 00:00:00
abstract:BACKGROUND:Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term stru...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2043-3
更新日期:2019-12-04 00:00:00
abstract:INTRODUCTION:There is inconsistent association between urate transporters SLC22A11 (organic anion transporter 4 (OAT4)) and SLC22A12 (urate transporter 1 (URAT1)) and risk of gout. New Zealand (NZ) Māori and Pacific Island people have higher serum urate and more severe gout than European people. The aim of this study w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4417
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Identification of risk factors for rapid joint destruction in early rheumatoid arthritis (RA) can be helpful for optimizing treatment, and improving our understanding of destructive arthritis and its mechanisms. The objective of this study was to investigate the relationship between early RA patient characte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1575-2
更新日期:2018-05-02 00:00:00
abstract::The present studies were initiated to determine the protein expression patterns of fibroblast-like synovial (FLS) cells derived from the synovia of rheumatoid arthritis patients. The cellular proteins were separated by two-dimensional polyacrylamide gel electrophoresis and the in-gel digested proteins were analyzed by...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1153
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:To aim was to investigate the additional value of incorporating the de Vlam cervical facet joint score in the modified ankylosing spondylitis (AS) spine score (mSASSS) for the evaluation of spinal radiographic outcome in AS. METHOD:Baseline and 4-year radiographs from 98 consecutive patients from the Gronin...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1285-1
更新日期:2017-04-26 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PC...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4086
更新日期:2012-11-08 00:00:00
abstract:BACKGROUND:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02324-7
更新日期:2020-10-15 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate cau...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3759
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:We aimed to understand the changes in cartilage lubricin expression and immunolocalisation in responsed to treadmill running with different intensities in a rat model. METHODS:A total of 24 male Wistar rats were randomly assigned into groups of control (CON), low-intensity running (LIR), moderate-intensit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4101
更新日期:2012-11-24 00:00:00
abstract::TNF receptor-associated periodic syndrome (TRAPS) is a dominantly inherited disease caused by missense mutations in the TNF receptor 1 (TNFR1) gene. Patients suffer from periodic bouts of severe abdominal pain, localised inflammation, migratory rashes, and fever. More than 40 individual mutations have been identified,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2197
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA). METHODS:Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3926
更新日期:2012-07-25 00:00:00