Abstract:
INTRODUCTION:Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration. METHODS:Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knock-out mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age. RESULTS:Early IVD degeneration involved significant changes in numerous pathways, including Wnt/β-catenin signaling. With regard to Wnt/β-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant down-regulation of axin2 gene expression. IVD degeneration involved significant down-regulation in Caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of wild-type mice was rich in viable NCs, whereas the NP of Caveolin-1 knock-out mice contained chondroid-like matrix with mainly apoptotic, small, rounded cells. CONCLUSIONS:Early IVD degeneration involves down-regulation of canonical Wnt signaling and Caveolin-1 expression, which appears to be essential to the physiology and preservation of NCs. Therefore, Caveolin-1 may be regarded an exciting target for developing strategies for IVD regeneration.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Smolders LA,Meij BP,Onis D,Riemers FM,Bergknut N,Wubbolts R,Grinwis GC,Houweling M,Groot Koerkamp MJ,van Leenen D,Holstege FC,Hazewinkel HA,Creemers LB,Penning LC,Tryfonidou MAdoi
10.1186/ar4157subject
Has Abstractpub_date
2013-01-29 00:00:00pages
R23issue
1eissn
1478-6354issn
1478-6362pii
ar4157journal_volume
15pub_type
杂志文章abstract:BACKGROUND:The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. METHODS:To generate expression of the CII-peptide sp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1037-7
更新日期:2016-06-14 00:00:00
abstract:BACKGROUND:Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disea...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析
doi:10.1186/s13075-018-1604-1
更新日期:2018-05-30 00:00:00
abstract:INTRODUCTION:Data from clinical studies on the long-term efficacy and safety of anti-tumor necrosis factor (TNF)-α therapy in patients with ankylosing spondylitis (AS) are scarce. This is the first report on continuous treatment with the TNFα fusion protein etanercept over seven years (y). METHODS:Overall, 26 patients...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4244
更新日期:2013-01-01 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:INTRODUCTION:Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. The fractional renal clearance of urate (FCU, renal clearance of urate/renal clearance of creatinine) has been proposed as a tool to identify subjects who manifest inefficient ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4020
更新日期:2012-08-17 00:00:00
abstract:INTRODUCTION:Notable weakness of the quadriceps muscles is typically observed as a consequence of knee joint arthritis, knee surgery and knee injury. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhib...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0724-0
更新日期:2015-08-12 00:00:00
abstract:INTRODUCTION:Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from A...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2929
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Enhanced B cell activity, particularly memory B cells have gained interest in evaluating response during therapies with biologics. CD27-IgD- double-negative (DN) B cells lacking the conventional memory marker CD27 are reported to be part of the memory compartment, however, only scarce data is available for...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0580-y
更新日期:2015-03-14 00:00:00
abstract::This review summarizes the immunological consequences of biological therapies used in juvenile idiopathic arthritis (JIA). For every frequently used biological agent the characteristics are clearly specified (molecular target, isotype, registered indication for JIA, route of administration, half-life, contraindication...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4213
更新日期:2013-01-01 00:00:00
abstract::Decreased number and impaired functions of endothelial progenitor cells (EPCs) leading to impaired vasculogenesis have been associated with rheumatoid arthritis (RA). Defective vasculogenesis has also been implicated in premature atherosclerosis in RA. Recently, early-outgrowth monocytic and late-outgrowth hemangiobla...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2943
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:A proliferation-inducing ligand (APRIL) from the TNF family, owing to its role in the generation and survival of plasma cells (PCs), is currently targeted for rheumatoid arthritis (RA) treatment. However, little is known about APRIL expression in RA lesions, hampering our understanding of the way APRIL may...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2817
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0865-1
更新日期:2015-12-05 00:00:00
abstract:BACKGROUND:Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). METHOD:RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously v...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1220-5
更新日期:2017-02-02 00:00:00
abstract:BACKGROUND:Synovial fibroblasts play a key role in joint destruction and regulation of the inflammatory infiltrate in established rheumatoid arthritis (RA). The mechanisms by which this occurs in the earliest stages of RA are largely unknown. We investigated the role of Dickkopf-related protein 1 (DKK1) produced by syn...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0915-3
更新日期:2016-01-19 00:00:00
abstract::Cardiovascular morbidity and mortality are becoming major health concerns for adults with inflammatory rheumatic diseases. The enhanced atherogenesis in this patient population is promoted by the exposure to traditional risk factors as well as nontraditional cardiovascular insults, such as corticosteroid therapy, chro...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4212
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Galectin-9 (Gal-9) is involved in the regulatory process of immune responses or inflammation. The aim of the present study is to characterize circulating Gal-9 in patients with rheumatoid arthritis (RA) and its relationship with RA disease activity and phenotype. METHODS:A total of 116 RA patients and 31 ag...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02158-3
更新日期:2020-04-15 00:00:00
abstract:INTRODUCTION:The objective of this study was to examine the association between occupation and osteoarthritis (OA) leading to total knee (TKR) or hip (THR) joint replacement. METHODS:The following is the case-control study design. All patients still living in Iceland who had had a TKR or THR due to OA as of the end of...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3033
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representat...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2519
更新日期:2008-01-01 00:00:00
abstract::TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA), particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness of TNF inhibitors as initial treatment for active RA. New data from...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2970
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Patients with recent-onset rheumatoid arthritis (RA) have impaired brachial artery endothelial function compared with controls matched for age, sex and cardiovascular risk factors. The present study examined endothelium-dependent (flow-mediated dilatation (FMD)) and independent (glyceryl trinitrate (GTN)-m...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2668
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Reconstitution of peripheral blood (PB) B cells after therapeutic depletion with the chimeric anti-CD20 antibody rituximab (RTX) mimics lymphatic ontogeny. In this situation, the repletion kinetics and migratory properties of distinct developmental B-cell stages and their correlation to disease activity mi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2686
更新日期:2009-01-01 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:INTRODUCTION:The role of adiponectin in the pathogenesis of arthritis is still controversial. This study was performed to examine whether adiponectin is involved in joint inflammation and destruction in rheumatoid arthritis (RA) in relation to the expression of vascular endothelial growth factor (VEGF) and matrix metal...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2844
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVES:Muckle-Wells syndrome (MWS) is an autoinflammatory disease characterized by excessive interleukin-1 (IL-1) release, resulting in recurrent fevers, sensorineural hearing loss, and amyloidosis. IL-1 inhibition with anakinra, an IL-1 receptor antagonist, improves clinical symptoms and inflammatory markers. Subc...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4237
更新日期:2013-01-01 00:00:00
abstract::Inflammation and inflammatory responses are modulated by a bidirectional communication between the neuroendocrine and immune system. Many lines of research have established the numerous routes by which the immune system and the central nervous system (CNS) communicate. The CNS signals the immune system through hormona...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1002
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3205
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3309
更新日期:2011-04-07 00:00:00
abstract:INTRODUCTION:miR-146a is one of the first identified miRNAs expressed differentially in osteoarthritis (OA) cartilage. However, the role it plays in OA pathogenesis is not clear. The aim of this study is to identify a molecular target of miR-146a, thereby elucidating its function in chondrocytes during OA pathogenesis....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3798
更新日期:2012-04-16 00:00:00
abstract:BACKGROUND:Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients w...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2018-4
更新日期:2019-11-27 00:00:00
abstract::It is well established that an intimate connection exists between inflammation and neoplasia. Indeed, particular chronic infections and autoimmune processes giving rise to prolonged site-specific inflammation are known to increase the probability of the development of specific cancers. Molecular characterisation of th...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4203
更新日期:2013-01-01 00:00:00