Abstract:
BACKGROUND:Metformin could activate adenosine monophosphate-activated protein kinase (AMPK) which was postulated as a potential therapeutic target for osteoarthritis. This study aimed to examine the effects of metformin on cartilage and pain in osteoarthritis mouse model. METHODS:Eighty 10-week-old male C57BL/6 mice were randomized to 6 groups: non-operation, sham-operation, destabilization of the medial meniscus (DMM)-operation with intragastric saline/metformin, and DMM-operation with intraarticular saline/metformin. Articular cartilage degeneration was examined by scanning electron microscopy (SEM) and graded using the scoring system recommended by Osteoarthritis Research Society International (OARSI). Mechanical withdrawal threshold and hind paw weight distribution were measured to assess the pain-related behavior. Cell Counting Kit-8 assay, quantificational real-time polymerase chain reaction, and western blot analysis were conducted to examine the anabolic and anti-catabolic effect of metformin and the role of AMPK in mediating its effects on interleukin-1β stimulated primary mice chondrocytes. RESULTS:Compared with mice receiving intragastric and intraarticular saline, mice in both intragastric and intraarticular metformin displayed attenuated articular cartilage degeneration, indicated by less cartilage damage under SEM and significantly lower OARSI scores. A higher paw withdrawal threshold and a decreased weight-bearing asymmetry were observed in the intragastric and intraarticular metformin mice compared with their corresponding saline groups in DMM model of osteoarthritis. In vitro experiments showed that metformin not only decreased the level of matrix metalloproteinase 13, but also elevated type II collagen production through activating AMPK pathway. CONCLUSIONS:Metformin attenuates osteoarthritis structural worsening and modulates pain, suggesting its potential for osteoarthritis prevention or treatment.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Li H,Ding X,Terkeltaub R,Lin H,Zhang Y,Zhou B,He K,Li K,Liu Z,Wei J,Yang Y,Xie H,Zeng C,Lei Gdoi
10.1186/s13075-020-2129-ysubject
Has Abstractpub_date
2020-02-22 00:00:00pages
34issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-020-2129-yjournal_volume
22pub_type
杂志文章abstract:BACKGROUND:The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of systemic lupus erythematosus (SLE) patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To overcom...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1117-8
更新日期:2016-10-04 00:00:00
abstract:INTRODUCTION:Lesional skin of patients with discoid lupus erythematosus (DLE) contains macrophages, whose polarization has yet to be investigated. To test our hypothesis that M1 macrophages would be increased in DLE skin, we examined transcriptome alterations in immune cell gene expression and macrophage features in DL...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0839-3
更新日期:2015-11-13 00:00:00
abstract::Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3251
更新日期:2011-03-17 00:00:00
abstract:BACKGROUND:The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to ex...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1332-y
更新日期:2017-06-02 00:00:00
abstract:INTRODUCTION:Cell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model. ME...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4156
更新日期:2013-01-29 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::The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease--the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2729
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Accumulation of advanced glycation end-products (AGEs) is involved in age-related osteoarthritis (OA). Glyoxalase (Glo)-1 is the main enzyme involved in the removal of AGE precursors, especially carboxymethyl-lysine (CML). We aimed to investigate the expression of several AGEs and Glo-1 in human OA cartilage...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1801-y
更新日期:2019-01-11 00:00:00
abstract::Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8+ T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial h...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1758
更新日期:2005-01-01 00:00:00
abstract::The antigens that trigger the pathogenic immune response in rheumatoid arthritis (RA) remain unknown. Until recently it was assumed that either viral or microbial antigens, or joint-specific antigens were the target of arthritogenic T and B lymphocytes in RA. Consequently, murine models of arthritis are induced by imm...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1476
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) patients have lower bone mineral density and increased fracture risk when compared with healthy individuals, due to distinct factors and mechanisms. Bone remodeling is a tightly orchestrated process dependent on several factors, including the balance between receptor acti...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar3500
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:The present study aimed to explore a possible role for IL-21 producing Th-cells in the immunopathogenesis of granulomatosis with polyangiitis (GPA). METHODS:Peripheral blood from 42 GPA patients in remission and 29 age-matched healthy controls (HCs) were stimulated in vitro, and the frequencies of IL-21 p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4247
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2581
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA-FLS) contribute to joint inflammation and damage characteristic of the disease. RA-FLS express KCa1.1 (BK, Slo1, MaxiK, KCNMA1) as their major plasma membrane potassium channel. Blocking KCa1.1 reduces the invasive phenotype of RA-FLS and attenua...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1003-4
更新日期:2016-05-10 00:00:00
abstract:BACKGROUND:The aim was to further characterize immunoglobulin G4-related disease (IgG4-RD) by a large-scale multicenter study of its clinical and laboratory features conducted by multidisciplinary physicians of IgG4-RD in Japan. METHODS:Various specialists retrospectively evaluated IgG4-RD patients diagnosed between 1...
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:BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-2133-2
更新日期:2020-03-27 00:00:00
abstract:INTRODUCTION:The purpose of this study was the evaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA). METHODS:Systemic and lo...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3090
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:To date, no single most-appropriate factor or delivery method has been identified for the purpose of mesenchymal stem cell (MSC)-based treatment of cartilage injury. Therefore, in this study we tested whether gene delivery of the growth factor Indian hedgehog (IHH) was able to induce chondrogenesis in huma...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3921
更新日期:2012-07-20 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a me...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1122-y
更新日期:2016-10-06 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
abstract:INTRODUCTION:TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-kappaB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently intro...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/ar2816
更新日期:2009-01-01 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::Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4035
更新日期:2012-09-28 00:00:00
abstract:INTRODUCTION:Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients wit...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3827
更新日期:2012-05-01 00:00:00
abstract:INTRODUCTION:Though remission is currently a treatment goal in patients with rheumatoid arthritis (RA), the number of patients who achieve and sustain remission in daily practice is still small. It is suggested that early remission will be associated with sustainability of remission. The aim was to study the associatio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3027
更新日期:2010-01-01 00:00:00
abstract::Advanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET)...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13075-014-0423-2
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA....
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-0982-5
更新日期:2016-04-12 00:00:00
abstract::Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3227
更新日期:2011-02-25 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:Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruct...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4474
更新日期:2014-02-05 00:00:00