Abstract:
INTRODUCTION:The present study examined the effect of C-type natriuretic peptide (CNP) on the anabolic and catabolic activities in chondrocyte/agarose constructs subjected to dynamic compression. METHODS:Constructs were cultured under free-swelling conditions or subjected to dynamic compression with low (0.1 to 100 pM) or high concentrations (1 to 1,000 nM) of CNP, interleukin-1β (IL-1β), and/or KT-5823 (inhibits cyclic GMP-dependent protein kinase II (PKGII)). Anabolic and catabolic activities were assessed as follows: nitric oxide (NO) and prostaglandin E2 (PGE2) release, and [3H]-thymidine and 35SO4 incorporation were quantified by using biochemical assays. Gene expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan, and collagen type II were assessed with real-time quantitative PCR (qPCR). Two-way ANOVA and the post hoc Bonferroni-corrected t tests were used to examine data. RESULTS:CNP reduced NO and PGE2 release and partially restored [3H]-thymidine and 35SO4 incorporation in constructs cultured with IL-1β. The response was dependent on the concentration of CNP, such that 100 pM increased [3H]-thymidine incorporation (P < 0.001). This is in contrast to 35SO4 incorporation, which was enhanced with 100 or 1000 nM CNP in the presence and absence of IL-1β (P < 0.001). Stimulation by both dynamic compression and CNP and/or the PKGII inhibitor further reduced NO and PGE2 release and restored [3H]-thymidine and 35SO4 incorporation. In the presence and absence of IL-1β, the magnitude of stimulation for [3H]-thymidine and 35SO4 incorporation by dynamic compression was dependent on the concentration of CNP and the response was inhibited with the PKGII inhibitor. In addition, stimulation by CNP and/or dynamic compression reduced IL-1β-induced iNOS and COX-2 expression and restored aggrecan and collagen type II expression. The catabolic response was not further influenced with the PKGII inhibitor in IL-1β-treated constructs. CONCLUSIONS:Treatment with CNP and dynamic compression increased anabolic activities and blocked catabolic effects induced by IL-1β. The anabolic response was PKGII mediated and raises important questions about the molecular mechanisms of CNP with mechanical signals in cartilage. Therapeutic agents like CNP could be administered in conjunction with controlled exercise therapy to slow the OA disease progression and to repair damaged cartilage. The findings from this research provide the potential for developing novel agents to slow the pathophysiologic mechanisms and to treat OA in the young and old.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Ramachandran M,Achan P,Salter DM,Bader DL,Chowdhury TTdoi
10.1186/ar3459subject
Has Abstractpub_date
2011-01-01 00:00:00pages
R145issue
5eissn
1478-6354issn
1478-6362pii
ar3459journal_volume
13pub_type
杂志文章abstract::The discovery of the receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) system and its role in the regulation of bone resorption exemplifies how both serendipity and a logic-based approach can identify factors that regulate cell function. Before this discovery in the mid to late 1990...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2165
更新日期:2007-01-01 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::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::A growing body of literature has demonstrated that the multifunctional glycoprotein osteopontin (OPN), has a role in type I interferon (IFN) production and may be involved in systemic lupus erythematosus (SLE) pathogenesis. A recent report has provided further support for this, demonstrating an association between rai...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar4172
更新日期:2013-03-08 00:00:00
abstract:BACKGROUND:Validated clinical prediction models to identify children with poor prognosis at the time of juvenile idiopathic arthritis (JIA) diagnosis would be very helpful for tailoring treatments, and avoiding under- or over-treatment. Our objective was to externally validate Nordic clinical prediction models in Canad...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2091-8
更新日期:2020-01-15 00:00:00
abstract:BACKGROUND:The aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies. METHODS:Patients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13075-018-1541-z
更新日期:2018-03-23 00:00:00
abstract::There is increasing recognition that central pain sensitivity plays an important role in pain severity among patients with osteoarthritis. Murphy and colleagues identified clusters of patients with osteoarthritis according to pain severity and accompanying symptoms, and one of these groups appeared to have a greater d...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3499
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1147-2
更新日期:2016-10-22 00:00:00
abstract:BACKGROUND:Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-017-1387-9
更新日期:2017-08-11 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: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::Inhibition of NF-kappaB is known to be effective in reducing both inflammation and bone destruction in animal models of arthritis. Our previous study demonstrated that a small cell-permeable NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), suppresses expression of proinflammatory cytokines and ameliorates ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2298
更新日期:2007-01-01 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::Unfortunately, after publication of this article [1], it was noticed that Fig. 2 is incorrect. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13075-018-1700-2
更新日期:2018-09-10 00:00:00
abstract:INTRODUCTION:The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS). ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3823
更新日期:2012-04-30 00:00:00
abstract:BACKGROUND:This study aimed at investigating the effect of a resistance exercise intervention on the interstitial muscle levels of pro-inflammatory cytokines in fibromyalgia (FMS) and healthy controls (CON). METHODS:Twenty-four female patients with FMS (54 ± 8 years) and 27 female CON (54 ± 9 years) were subjected to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13075-016-1041-y
更新日期:2016-06-13 00:00:00
abstract:BACKGROUND:Osteoarthritis (OA) is a whole joint disease that affects all joint tissues, with changes in the articular cartilage (AC), subchondral bone and synovium. Pathologies in menisci and ligaments, however, are rarely analysed, although both are known to play vital roles in the mechanical stability of the joint. T...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02261-5
更新日期:2020-07-16 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::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::A considerable amount of research time has been invested in studies aimed at elucidating pathogenic processes in systemic sclerosis (SSc). Despite this, major challenges for biomedical science remain, such as identification of the key factors that determine susceptibility to SSc, and elucidation of the precise nature ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2186
更新日期:2007-01-01 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
abstract::Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1458
更新日期:2005-01-01 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::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:RESULTS:Anti-CarP antibodies were detected in 117 patients with RA (37.9%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were...
journal_title:Arthritis research & therapy
pub_type: 已发布勘误
doi:10.1186/s13075-016-1205-9
更新日期:2016-12-16 00:00:00
abstract:INTRODUCTION:Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselecte...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0756-5
更新日期:2015-08-28 00:00:00
abstract:INTRODUCTION:The non-histone nuclear protein high mobility group box protein-1 (HMGB1) is typically associated with nucleosomes, but may shuttle between the nucleus and the cytoplasm, and under some conditions also be released extracellularly and participate in systemic inflammation. Monoclonal HMGB1-targeting antibodi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0856-2
更新日期:2015-11-23 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:INTRODUCTION:We and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines ye...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3237
更新日期:2011-02-03 00:00:00
abstract:INTRODUCTION:Patients with rheumatoid arthritis (RA) are at an increased risk of malignancies compared with the general population. This has raised concerns regarding these patients, particularly with the widespread use of immunomodulating therapies, including biologic disease-modifying antirheumatic drugs (DMARDs). We...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s13075-015-0728-9
更新日期:2015-08-15 00:00:00