Abstract:
BACKGROUND:Intervertebral disc degeneration (IVDD)-related disorders are the major causes of low back pain. A previous study suggested that Notch activation serves as a protective mechanism and is a part of the compensatory response that maintains the necessary resident nucleus pulposus (NP) cell proliferation to replace lost or non-functional cells. However, the exact mechanism remains to be determined. In this study, we aimed to investigate the role of JAG2/Notch2 in NP cell proliferation and apoptosis. METHODS:Recombinant JAG2 or Notch2, Hes1, and Hey2 siRNAs were used to activate or inhibit Notch signaling. Cell proliferation, apoptosis, cell cycle regulatory factors, and pathways associated with Notch-mediated proliferation were examined. In vivo experiments involving an intradiscal injection of Sprague-Dawley rats were performed. RESULTS:Recombinant JAG2 induced Notch2 and Hes1/Hey2 expression together with NP cell proliferation. Downregulation of Notch2/Hes1/Hey2 induced G0/G1 phase cell cycle arrest in NP cells. Moreover, Notch2 mediated NP cell proliferation by regulating cyclin D1 and by activating PI3K/Akt and Wnt/β-catenin signaling. Furthermore, Notch signaling inhibited TNF-α-promoted NP cell apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Finally, we found that intradiscal injection of JAG2 alleviated IVDD and that sh-Notch2 aggravated IVDD in a rat model. These results indicated that JAG2/Notch2 inhibited IVDD by modulating cell proliferation, apoptosis, and extracellular matrix. The JAG2/Notch2 axis regulated NP cell proliferation via PI3K/Akt and Wnt/β-catenin signaling and inhibited TNF-α-induced apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. CONCLUSIONS:The current and previous results shed light on the therapeutic implications of targeting the JAG2/Notch2 axis to inhibit or reverse IVDD.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Long J,Wang X,Du X,Pan H,Wang J,Li Z,Liu H,Li X,Zheng Zdoi
10.1186/s13075-019-1990-zsubject
Has Abstractpub_date
2019-10-16 00:00:00pages
213issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-019-1990-zjournal_volume
21pub_type
杂志文章abstract:INTRODUCTION:Ankylosing spondylitis (AS) is an inflammatory disease associated with new bone formation and an increased risk of osteoporosis and fractures. The negative effects of AS on bone microarchitecture and strength are unclear. Thus, we conducted an observational study to analyze the effect of AS on bone microar...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0873-1
更新日期:2015-12-24 00:00:00
abstract:INTRODUCTION:A number of occupational risk factors are discussed in relation to the development and progress of knee joint diseases (for example, working in a kneeling or squatting posture, lifting and carrying heavy weights). Besides the occupational factors, a number of individual risk factors are important. The dist...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3015
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patien...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1578-z
更新日期:2018-05-02 00:00:00
abstract::The changes occurring in the field of rheumatoid arthritis (RA) over the past decade or two have encompassed new therapies and, in particular, a new look at the clinical characteristics of the disease in the context of therapeutic improvements. It has been shown that composite disease activity indices have special mer...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2535
更新日期:2009-01-01 00:00:00
abstract::Patients with lupus have a continuous production of IFNα and display an increased expression of IFNα-regulated genes. The reason for the ongoing IFNα synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2884
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote collagen I (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0411-6
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. METHOD:Assessm...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-019-2055-z
更新日期:2019-12-04 00:00:00
abstract::The field of biomarkers is a growing one, particularly in osteoarthritis (OA). OA is the most common disabling condition in older persons and a major cause of morbidity. While the debate continues about which of the involved tissues--cartilage, bone or synovium--is the most important in OA aetiology, there is no doubt...
journal_title:Arthritis research & therapy
pub_type: 评论,社论,评审
doi:10.1186/ar2839
更新日期:2009-01-01 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
abstract:INTRODUCTION:Monocytic cells play a central role in the aetiology of rheumatoid arthritis, and manipulation of the activation of these cells is an approach currently under investigation to discover new therapies for this and associated diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed in ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4288
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:The efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS. METHODS:The Cochrane Library, EMBASE, MEDLINE, PsychInfo and SPORTDISCUS (through April 2009) and the re...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/ar3002
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02351-4
更新日期:2020-10-19 00:00:00
abstract::We investigated the therapeutic potential and mechanism of action of IFN-beta protein for the treatment of rheumatoid arthritis (RA). Collagen-induced arthritis was induced in DBA/1 mice. At the first clinical sign of disease, mice were given daily injections of recombinant mouse IFN-beta or saline for 7 days. Disease...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1165
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Microchimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN. METHODS:Twenty-seven renal biopsies we...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0615-4
更新日期:2015-04-15 00:00:00
abstract::Following publication of the original article [1], the authors reported a typesetting error. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13075-018-1753-2
更新日期:2018-11-05 00:00:00
abstract:BACKGROUND:The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantib...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1061-7
更新日期:2016-07-07 00:00:00
abstract:INTRODUCTION:Our objective was to examine the role of the janus-activated kinase (JAK) pathway in the modulation of tumor necrosis factor-α (TNF)-induced-IL-18 bioactivity by reduction of caspase-1 function. METHODS:Caspase-1 expression in rheumatoid arthritis (RA) synovial fibroblasts treated with TNF was assessed by...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4551
更新日期:2014-04-24 00:00:00
abstract:BACKGROUND:Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular c...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02354-1
更新日期:2020-12-09 00:00:00
abstract:INTRODUCTION:In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren's syndrome (pSS) and to identify predictors of response to treatment. METHODS:Sequential blood lymphocyte subsets and LSG b...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0750-y
更新日期:2015-09-04 00:00:00
abstract:INTRODUCTION:Vagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarc...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-015-0667-5
更新日期:2015-06-07 00:00:00
abstract:INTRODUCTION:Mutations in the NLRP3 gene are associated with the dominantly inherited cryopyrin-associated periodic syndrome (CAPS). The significance of the V198M variant is unclear; it has been reported in association with various CAPS phenotypes and as a variant of uncertain consequence. The aim of this study was to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4171
更新日期:2013-02-19 00:00:00
abstract::Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3657
更新日期:2012-01-30 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:INTRODUCTION:Rheumatoid arthritis (RA) is a chronic inflammatory and destructive disease of the joint. The synovial lining consists of two main types of cells: synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFα stimulates RA synovial fibroblasts to proliferate and produce growth factors, chemoki...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3778
更新日期:2012-03-14 00:00:00
abstract::This article is about risk. Risk is probably the most misunderstood component in determining therapeutic intervention; however, it is probably the most relevant issue to consider in the context of expected benefit. The rarity of quantitative risk-benefit assessment and the lack of comparative risk-benefit when alterna...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1924
更新日期:2006-01-01 00:00:00
abstract::Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction distur...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1848
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Mesenchymal stem cells (MSCs) can differentiate into various connective tissue cells. Several techniques have been used for the clinical application of MSCs in articular cartilage repair; however, there are many issues associated with the selection of the scaffold material, including its ability to support...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3735
更新日期:2012-02-07 00:00:00
abstract:BACKGROUND:Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H2S) has been implicated in mineralization but has never been studied in OA. Here, we investigated t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02147-6
更新日期:2020-03-17 00:00:00
abstract::Glucocorticoids have successfully been used in the treatment of rheumatoid arthritis. Data suggest that 7alpha-hydroxy-dehydroepiandrosterone (7alpha-OH-DHEA), an immunostimulating metabolite of dehydroepiandrosterone, can block glucocorticoid-induced immune suppression. Formation of 7alpha-OH-DHEA is catalyzed by act...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1819
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Porphyromonas gingivalis (Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria (i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02348-z
更新日期:2020-10-19 00:00:00