Abstract:
OBJECTIVES:Autophagy has recently been shown to regulate osteoclast activity and osteoclast differentiation. Here, we aim to investigate the impact of autophagy inhibition as a potential therapeutic approach for the treatment of osteoporosis in preclinical models. METHODS:Systemic bone loss was induced in mice by glucocorticoids and by ovariectomy (OVX). Autophagy was targeted by conditional inactivation of autophagy-related gene 7 (Atg7) and by treatment with chloroquine (CQ). Bone density was evaluated by microCT. The role of autophagy on osteoclastogenesis was analysed by osteoclastogenesis and bone resorption assays. The quantification of receptor activator of nuclear factor κ B ligand and osteoprotegerin proteins in cocultures was performed using ELISA whereas that of osteoclast and osteoblast differentiation markers was by qPCR. RESULTS:Selective deletion of Atg7 in monocytes from Atg7(fl/fl)_x_LysM-Cre mice mitigated glucocorticoid-induced and OVX-induced osteoclast differentiation and bone loss compared with Atg7(fl/fl) littermates. Pharmacological inhibition of autophagy by treatment with CQ suppressed glucocorticoid-induced osteoclastogenesis and protected mice from bone loss. Similarly, inactivation of autophagy shielded mice from OVX-induced bone loss. Inhibition of autophagy led to decreased osteoclast differentiation with lower expression of osteoclast markers such as NFATc1, tartrate-resistant acid phosphatase, OSCAR and cathepsin K and attenuated bone resorption in vitro. In contrast, osteoblast differentiation was not affected by inhibition of autophagy. CONCLUSIONS:Pharmacological or genetic inactivation of autophagy ameliorated glucocorticoid-induced and OVX-induced bone loss by inhibiting osteoclastogenesis. These findings may have direct translational implications for the treatment of osteoporosis, since inhibitors of autophagy such as CQ are already in clinical use.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
Lin NY,Chen CW,Kagwiria R,Liang R,Beyer C,Distler A,Luther J,Engelke K,Schett G,Distler JHdoi
10.1136/annrheumdis-2015-207240subject
Has Abstractpub_date
2016-06-01 00:00:00pages
1203-10issue
6eissn
0003-4967issn
1468-2060pii
annrheumdis-2015-207240journal_volume
75pub_type
杂志文章abstract::The CAMERA study shows that using methotrexate in a tight control setting might lead to considerable improvement in disease activity in early rheumatoid arthritis See linked article p 1443. ...
journal_title:Annals of the rheumatic diseases
pub_type: 评论,社论
doi:10.1136/ard.2007.076463
更新日期:2007-11-01 00:00:00
abstract:OBJECTIVE:To evaluate the nature of positional changes of humeroulnar (HU) and humeroradial (HR) joints in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA) followed up prospectively. METHODS:At the 15 year follow up standard anteroposterior and lateral radiographs of 148 elbow joints wer...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.8.765
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). OBJECTIVES:To investigate the analgesic potential of a modified version of osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) in the monosodium iodoacetate (MIA) model of OA pain. METHODS:Male Sprague Dawley rats (140-260 g) were...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-203260
更新日期:2014-08-01 00:00:00
abstract:OBJECTIVE:To assess the effects of tumour necrosis factor (TNF) antagonist therapy on B lymphocyte stimulator (BLyS) expression in patients with rheumatoid arthritis (RA). METHODS:Blood from 38 patients with RA from a single centre was collected prior to and following initiation of TNF antagonist therapy. Plasma BLyS ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.079954
更新日期:2008-08-01 00:00:00
abstract::We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-beta induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix p...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.073809
更新日期:2008-04-01 00:00:00
abstract::The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2012-202715
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVES:In juvenile idiopathic arthritis (JIA), the efficacy of very early disease-modifying drug therapy, synthetic or biological, is not well known. Three alternative strategies were compared for treating recent-onset polyarticular JIA. METHODS:In a 54-week multicentre open-label clinical trial, 60 disease-modify...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/ard.2010.143347
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVE:To evaluate the presence of flow by Doppler ultrasound (DUS) in the wrist and finger joints (carpometacarpal 1 (CMC1), metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints) of healthy controls. METHODS:Twenty seven healthy volunteers (15 women, 12 men; mean age 45 years, range 18-93) with a t...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.009548
更新日期:2004-06-01 00:00:00
abstract:OBJECTIVES:To study whether hand osteoarthritis (OA) is associated with increased mortality and cardiovascular events in a large community based cohort (Framingham Heart Study) in which OA, mortality and cardiovascular events have been carefully assessed. METHODS:We examined whether symptomatic (≥1 joint(s) with radio...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-203789
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Chronic systemic inflammation may contribute to accelerated atherosclerosis and increased arterial stiffness in patients with rheumatoid arthritis (RA). In addition to lowering cholesterol, statins have immunomodulatory effects which may be especially beneficial in patients with RA who have systemic immune a...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.018333
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVE:To review the presentation and clinical findings of arthritis associated with hidradenitis suppurativa. METHOD:Medical records from the rheumatology clinics of two major teaching hospitals were reviewed for arthritis and hidradenitis suppurativa. The nine patient records fulfilling these criteria were review...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.53.1.64
更新日期:1994-01-01 00:00:00
abstract::One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. The nature of this serum factor is unclear, but has been suggested to be a lipoprotein. Sera from patients with (1) systemic necrotising arteritis (polyarter...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.3.176
更新日期:1985-03-01 00:00:00
abstract:OBJECTIVES:To evaluate coronary atherosclerosis in patients with psoriatic arthritis (PsA) and control subjects using coronary CT angiography (CCTA). METHODS:Ninety consecutive patients with PsA (male: 56(62.2%); 50.3±11.1 years) were recruited. 240 controls (male: 137(57.1%); 49.6±10.7 years) without known cardiovasc...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2016-210390
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Small studies have linked α1 antitrypsin (α1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). OBJECTIVE:To test the validity and the mechanism of this association between α1AT and AAV. METHODS:The distribution of α1AT deficiency alleles Z and S was co...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
doi:10.1136/ard.2011.153569
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVES:Systemic immunological processes are profoundly shaped by the micro-environments where antigen recognition occurs. Identifying molecular signatures distinctive of such processes is pivotal to understand pathogenic immune responses and manipulate them for therapeutic purposes. Unfortunately, direct investigat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206226
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. METHODS:Synovial biopsies were obtained from pat...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2014-206921
更新日期:2016-04-01 00:00:00
abstract::Management of ankylosing spondylitis (AS) is challenged by the progressive nature of the disease. To date, no intervention is available that alters the underlying mechanism of inflammation in AS. Currently available conventional treatments are palliative at best, and often fail to control symptoms in the long term. Cu...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/ard.61.suppl_3.iii40
更新日期:2002-12-01 00:00:00
abstract::Of 29 524 hospitalised medical patients monitored in a drug surveillance programme 1835 (6.2%) received the xanthine oxidase inhibitor allopurinol. After the exclusion of skin reactions adverse effects were attributed to this drug in 33 (1.8%) patients, the most frequent being haematological abnormalities (11 patients...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.40.3.245
更新日期:1981-06-01 00:00:00
abstract:OBJECTIVE:To evaluate the effects of infliximab and corticosteroid treatment on the lipid profile in patients with active rheumatoid arthritis (RA). METHODS:Infliximab infusions were given at weeks 0, 2, 6 and then every 8 weeks. Before each infusion, disease activity parameters (Disease Activity Index 28-Joint Score ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2006.059691
更新日期:2007-07-01 00:00:00
abstract:OBJECTIVE:To develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice. METHODS:Candidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi surv...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2015-208671
更新日期:2016-06-01 00:00:00
abstract:OBJECTIVE:To examine the association between body mass index (BMI) and osteoarthritis (OA) leading to total hip (THR) or knee (TKR) joint replacement. METHODS:Case-control study design. All patients still living in Iceland who had had a THR or TKR resulting from OA before the end of 2002 were invited to participate. F...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2007.086868
更新日期:2009-04-01 00:00:00
abstract::We studied the course of adjuvant arthritis in rats by measuring clinical, biochemical, and histological parameters on day 36 after induction (representing the secondary reaction) and on day 171, which is at the stage of permanent deformity. The effect of SR 41319, a new diphosphonate, was evaluated on days 36 and 171...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.45.1.67
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years. OBJECTIVE:To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk f...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2011-200668
更新日期:2012-06-01 00:00:00
abstract::False positive results were obtained for HIV tests in two men with active systemic lupus erythematosus (SLE) who were suspected of being infected with HIV because of fever, weight loss, lymphadenopathy, and inflammatory myopathy. Enzyme linked immunosorbent assays (ELISAs) for HIV were twice positive when tested three...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.51.9.1071
更新日期:1992-09-01 00:00:00
abstract::Eighty-one patients with 116 osteoarthritic knees were seen by the author at the University College Hospital (UCH), Ibadan in six years. Below the age of 50 the disease was significantly commoner among Nigerians than Caucasians; 39.5% of our patients were less than 50 years old, compared with 1.1% of Caucasians. In co...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.44.10.682
更新日期:1985-10-01 00:00:00
abstract:OBJECTIVE:The technique and results of a special oblique radiograph of the hip called the "faux profil" (FP) of the hip are described. The FP was evaluated for the detection of joint space narrowing in incipient osteoarthritis of the hip (OAH) as compared with the anteroposterior (AP) radiograph. METHODS:58 hips with ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.57.11.676
更新日期:1998-11-01 00:00:00
abstract:OBJECTIVES:To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. METHODS:Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2017-212935
更新日期:2018-08-01 00:00:00
abstract::This review assesses the risk assessment of cardiovascular disease (CVD) in rheumatoid arthritis (RA) and how non-invasive imaging modalities may improve risk stratification in future. RA is common and patients are at greater risk of CVD than the general population. Cardiovascular (CV) risk stratification is recommend...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,评审
doi:10.1136/annrheumdis-2016-209744
更新日期:2017-07-01 00:00:00
abstract:OBJECTIVE:The expression of antinuclear antibodies (ANA) is considered almost constant in systemic lupus erythematosus (SLE), although recent experience has suggested that many subjects with SLE considered for clinical trials are ANA negative at screening. The objective of this study is to determine whether assay varia...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2017-212599
更新日期:2018-06-01 00:00:00
abstract:OBJECTIVES:To determine the relevance of calpain in murine collagen induced arthritis (CIA) and to correlate the presence of m-calpain with the appearance of arthritis and cartilage destruction. METHODS:The immunohistochemical appearance and localisation of m-calpain at different stages of arthritis were analysed and ...
journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.54.6.477
更新日期:1995-06-01 00:00:00