Abstract:
INTRODUCTION:Standard measurements used to assess murine models of rheumatoid arthritis, notably paw thickness and clinical score, do not align well with certain aspects of disease severity as assessed by histopathology. We tested the hypothesis that non-invasive optical tomographic imaging of molecular biomarkers of inflammation and bone turnover would provide a superior quantitative readout and would discriminate between a disease-modifying anti-rheumatic drug (DMARD) and a non-DMARD treatment. METHODS:Using two protease-activated near-infrared fluorescence imaging agents to detect inflammation-associated cathepsin and matrix metalloprotease activity, and a third agent to detect bone turnover, we quantified fluorescence in paws of mice with collagen antibody-induced arthritis. Fluorescence molecular tomographic (FMT) imaging results, which provided deep tissue detection and quantitative readouts in absolute picomoles of agent fluorescence per paw, were compared with paw swelling, clinical scores, a panel of plasma biomarkers, and histopathology to discriminate between steroid (prednisolone), DMARD (p38 mitogen-activated protein kinase (MAPK) inhibitor) and non-DMARD (celecoxib, cyclooxygenase-2 (COX-2) inhibitor) treatments. RESULTS:Paw thickness, clinical score, and plasma biomarkers failed to discriminate well between a p38 MAPK inhibitor and a COX-2 inhibitor. In contrast, FMT quantification using near-infrared agents to detect protease activity or bone resorption yielded a clear discrimination between the different classes of therapeutics. FMT results agreed well with inflammation scores, and both imaging and histopathology provided clearer discrimination between treatments as compared with paw swelling, clinical score, and serum biomarker readouts. CONCLUSIONS:Non-invasive optical tomographic imaging offers a unique approach to monitoring disease pathogenesis and correlates with histopathology assessment of joint inflammation and bone resorption. The specific use of optical tomography allowed accurate three-dimensional imaging, quantitation in picomoles rather than intensity or relative fluorescence, and, for the first time, showed that non-invasive imaging assessment can predict the pathologist's histology inflammation scoring and discriminate DMARD from non-DMARD activity.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Peterson JD,Labranche TP,Vasquez KO,Kossodo S,Melton M,Rader R,Listello JT,Abrams MA,Misko TPdoi
10.1186/ar3038subject
Has Abstractpub_date
2010-01-01 00:00:00pages
R105issue
3eissn
1478-6354issn
1478-6362pii
ar3038journal_volume
12pub_type
杂志文章abstract:INTRODUCTION:C-reactive protein (CRP) is one of the biomarkers for the diagnosis and assessment of disease activity in rheumatoid arthritis (RA). CRP is not only the by-product of inflammatory response, but also plays proinflammatory and prothrombotic roles. The aim of this study was to determine the role of CRP on bon...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0563-z
更新日期:2015-03-04 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
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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
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0575-8
更新日期:2015-03-23 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2198
更新日期:2007-01-01 00:00:00
abstract::It has long been recognized that laboratory tests are useful in the diagnosis of disease and to monitor treatment outcome. Their performance has become even more demanding with the development of personalized medicine. In patients with rheumatoid arthritis (RA) the standard biochemical tests measure serological marker...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar3308
更新日期:2011-04-27 00:00:00
abstract:BACKGROUND:Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses. METHODS:A case-control study was co...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-019-2066-9
更新日期:2019-12-16 00:00:00
abstract:BACKGROUND:Clinical remission can be maintained after the discontinuation of biological disease-modifying antirheumatic drugs (bDMARDs) in some patients with rheumatoid arthritis (RA) (bDMARD-free remission (BFR)). It is unknown which bDMARD is advantageous for achieving BFR or under which conditions BFR can be conside...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-018-1673-1
更新日期:2018-08-03 00:00:00
abstract:INTRODUCTION:Although rheumatoid arthritis (RA) is generally a chronic disease, a proportion of RA-patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission, reflecting loss of disease-persistence. To explore mechanisms underlying RA-persistence, we performed a candidate gene study. We hypo...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0739-6
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13075-017-1467-x
更新日期:2017-12-01 00:00:00
abstract:INTRODUCTION:Autoantibodies in patients with polymyositis/dermatomyositis (PM/DM) are associated with unique subsets, clinical course and outcome. Anti-MJ antibodies, which recognize the nuclear protein NXP-2/MORC3, are reported in ~25% of juvenile DM. Prevalence and clinical significance of anti-MJ antibodies in adult...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3822
更新日期:2012-04-30 00:00:00
abstract:BACKGROUND:The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA pa...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1591-2
更新日期:2018-05-03 00:00:00
abstract::miRNAs have been shown to play essential regulatory roles in the innate immune system. They function at multiple levels to shape the innate immune response and maintain homeostasis by direct suppression of the expression of their target proteins, preferentially crucial signaling components and transcription factors. S...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4194
更新日期:2013-04-09 00:00:00
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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/s13075-018-1610-3
更新日期:2018-06-07 00:00:00
abstract::Pleiotropic effects are now described for the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (or statins) that might have utility in the context of chronic inflammatory autoimmune disease. Here we discuss the pharmacology and established uses of statins and in this context describe potential anti-inflammat...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1496
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:To analyze whether ANA-positive idiopathic anterior uveitis differs from JIA-associated uveitis concerning clinical course, response to treatment, and disease outcome. METHODS:Prospective study of the National Paediatric Rheumatological Database (NPRD) including its uveitis add-on module from the years 2002...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02166-3
更新日期:2020-04-15 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: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:Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies and immune complex deposition in various organs. Aberrations in the T lymphocyte compartment and dysregulated cytokine production are key features of SLE pathogenesis and disease progression. Recently...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3194
更新日期:2010-01-01 00:00:00
abstract::Articular calcification correlates with osteoarthritis (OA) severity but its exact role in the disease process is unclear. In examining OA meniscal cell function, Sun and colleagues have shown recently that meniscal cells from end-stage OA subjects can generate calcium crystals and that genes involved in calcification...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar2993
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades adjacent cartilage and bone in rheumatoid arthritis (RA). The study was undertaken to determine the effect of interleukin-17 (IL-17) on the survival and/or proliferation of FLSs from RA patients and to investigate wh...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4179
更新日期:2013-02-20 00:00:00
abstract::Irreversible destruction of joint structures is a major feature of osteoarthritis and rheumatoid arthritis. Fibrillar collagens in bone, cartilage and other soft tissues are critical for optimal joint form and function. Several approaches can be used to ascertain the role of collagenases, matrix metalloproteinases, in...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar600
更新日期:2003-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02157-4
更新日期:2020-03-24 00:00:00
abstract:INTRODUCTION:The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA. METHODS:A cross-sectional analysis was conducted on 3,591 individuals (66% Caucasian and 34...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3492
更新日期:2011-01-01 00:00:00
abstract::Most authorities recommend starting biological agents upon failure of at least one disease-modifying agent in patients with rheumatoid arthritis. However, owing to the absence of head-to-head studies, there is little guidance about which biological to select. Still, the practicing clinician has to decide. This review ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3149
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Galactosylation of immunoglobulin G (IgG) is reduced in rheumatoid arthritis (RA) and assumed to correlate with inflammation and altered humoral immunity. IgG hypogalactosylation also increases with age. To investigate dependencies in more detail, we compared IgG hypogalactosylation between patients with RA,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1540-0
更新日期:2018-03-14 00:00:00
abstract:INTRODUCTION:Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0531-7
更新日期:2015-03-05 00:00:00
abstract:INTRODUCTION:The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjögren's syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4442
更新日期:2014-01-17 00:00:00
abstract::Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can b...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3046
更新日期:2010-01-01 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