Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity

Chen, Chia Hsiang; Lin, Kuan Chia; Yu, David Tak Yan; Yang, Chunhua; Huang, Feng; Chen, H.-A.; Liang, Toong Hua; Liao, Hsien‐Tzung; Tsai, Chang Youh; Wei, James Cheng‐Chung; Chou, Chung Tei

doi:10.1093/rheumatology/kei208

Cited by 95 publications

(77 citation statements)

References 27 publications

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“…Two additional studies were removed after further assessment. Finally, 13 case-control studies were analyzed in the current meta-analysis (Yang et al, 2004b;Chen et al, 2006;de Seny et al, 2008;Lin et al, 2008;Sun and Yang, 2008;Wendling et al, 2008;Wang et al, 2010;Shen et al, 2011;Ma and Yang, 2012;Soliman et al, 2012;Dhir et al, 2013;Sha and Lei, 2013;Hou et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Serum matrix metalloproteinases-3 levels in patients with ankylosing spondylitis

Jw¹,

Kf²,

Js³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Cumulated evidence indicates that matrix metalloproteinase-3 (MMP-3) is significantly involved in cancer progression. Recent studies yielded conflicting results regarding the association between serum MMP-3 and ankylosing spondylitis (AS). To clarify this correlation, we performed a meta-analysis. Potential relevant studies were identified by searching the following databases: PubMed, Embase, CINAHL, Science Citation Index database, the Cochrane Library, Current Contents Index, Chinese Biomedical, the Chinese Journal Full-Text, and the Weipu Journal. Data from eligible studies were extracted and included into the meta-analysis using a random-effect model. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to assess the association between serum MMP-3 levels and AS. Thirteen case-control studies, including 707 AS cases and 442 healthy controls, were selected for the meta-analysis. The results indicate a significantly higher serum MMP-3 level in patients with AS than that in the controls (cases vs controls: SMD = 1.31, 95%CI = 0.84-1.78, P < 0.001). Ethnicity-subgroup analysis indicated a higher MMP-3 level in Asian and Caucasian patients with AS (all P < 0.05). This meta-analysis indicates that increased serum MMP-3

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Section: Discussionmentioning

confidence: 99%

Serum matrix metalloproteinases-3 levels in patients with ankylosing spondylitis

Jw¹,

Kf²,

Js³

et al. 2015

Genet. Mol. Res.

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“…7,8 Serum MMP-3, a key enzyme in ECM remodeling, is strongly elevated in AS patients. 9,10 Increased turnover of several different MMP-derived collagen species has been accepted as a main feature of AS. 11 Transforming growth factor-b1 (TGF-b1), the major form of TGF-b expressed in the immune system, is a multifunctional cytokine that plays a critical role in inflammation.…”

Section: Introductionmentioning

confidence: 99%

Histopathological changes in supraspinous ligaments, ligamentum flava and paraspinal muscle tissues of patients with ankylosing spondylitis

Zhang

et al. 2014

Int J of Rheum Dis

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Objective: To examine the histopathological changes in spinal tissues of ankylosing spondylitis (AS) patients.Methods: Tissue samples from 10 AS patients and 10 control subjects were obtained. Hematoxylin and eosin, picrosirius, Masson and van Gieson stainings were utilized to determine the pathological changes in tissues. Ultrastructural alterations were examined by electronic microscopy. Proteoglycan levels were assessed by enzyme-linked immunosorbent assays (ELISA). Matrix metalloproteinase-3 (MMP-3), transforming growth factor-b1 (TGF-b1) and tumor necrosis factor-a (TNF-a) levels were evaluated by immunohistochemistry.Results: Our results demonstrate that the density of collagen fibrils was reduced in the supraspinous ligaments of AS tissue and fibrils were loosely and irregularly organized as compared to a regular distribution of collagen fibrils in controls. In ligamentum flava from AS patients, activated fibroblasts with enlarged nuclei were detected, while the number of elastic fibers was greatly decreased. Paraspinal muscle tissues of AS patients exhibited increased collagen fibril accumulation and atrophy. Significantly decreased proteoglycan and elevated MMP-3 levels were found in supraspinous ligament samples from AS patients (P < 0.01). Additionally, the levels of TGF-b1 in ligamentum flava and paraspinal muscle tissues of AS patients were increased (P < 0.01). The expression of TNF-a was also upregulated in the ligamentum flavum (P < 0.01), with no significant difference in the paraspinal muscle between control and AS patients (P > 0.05).Conclusions: Our findings reveal histopathological changes that occur in certain spinal tissues of AS patients and suggest that increased levels of MMP-3 and TGF-b1 may contribute to the pathogenesis of AS.

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“…MMP-3 has been reported to reflect degree of inflammation [32] and correlate with disease activity in AS [33] and radiographic progression [34]. MMP-3 is involved in degradation of extracellular matrix proteins and is involved in degradation of cartilage and bone of inflamed joints [35].…”

Section: Discussionmentioning

confidence: 99%

A Prospective Double Blind Placebo Controlled Trial of Combination Disease Modifying Antirheumatic Drugs vs. Monotherapy (Sulfasalazine) in Patients with Inflammatory Low Backache in Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy

Vishad¹

2015

J Arthritis

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IntroductionSeronegative Spondyloarthropathies (SpA) refer to a group of chronic inflammatory disorders of unknown etiology. With prevalence between 0.5-2.5 percent, they are among the most common rheumatologic disorders [1]. This is a male predominant disease with a mean age of onset usually in the second and third decade. This includes a heterogeneous group of patients with predominant axial skeletal and entheseal involvement to more wide spread peripheral involvement; asymmetric or symmetric oligo/polyarthritis without any axial involvement. The subgroups which come under this terminology includes: Ankylosing Spondylitis (AS), Psoriatic Arthritis, Reactive Arthritis, Inflammatory bowel disease associated arthritis and Undifferentiated Spondyloarthritis (USpA).These diseases are major cause of morbidity for the patients, causing pain, stiffness, loss of mobility, disability, poor sleep and overall poor quality of life. In a study conducted by Linden et al., it was found that work related indices such as percentage of unemployment, lack of permanence of work, number of sick leaves and early retirement due to illness were all higher in patients with AS as compared to healthy individuals [2]. In another study, it was demonstrated that the quality of life in these patients is worse than cancer and myocardial infarction patients [3]. Amor et al., concluded that predictive factors of long term outcome could be defined very early after the onset of spondyloarthropathy [4]. It has been demonstrated that a major factor which influences the quality of life is the extent of entheseal involvement and associated stiffness and pain [5]. Besides these, the economic impact of loss of productivity due to AS calculated in terms of average annual human capital lost varies from Euros 4227 to Euros 8862 per patient.NSAIDS have been the main stay of treatment for these diseases for long. Despite providing good pain relief, they are largely ineffective in altering the natural course. However, very often, in spite of therapy, pain and discomfort continues in these patients with recurrent exacerbations.The DMARDs (Disease Modifying Anti Rheumatic Drugs) are a group of drugs which have come into prominence following their remarkable efficacy in the management of rheumatoid arthritis. The major drugs representative of this group are; methotrexate (MTX), Results:Of thirty three patients (31 males) with mean disease duration 39 months and mean BASDAI of 6 at baseline, 27 completed the study (16 in Combination DMARD and 11 in SSZ monotherapy group). ASAS 20 response, was achieved in 68.4% (13/19) and 50% (7/14) in the Combination DMARD and SSZ monotherapy groups (p=0.47), respectively. BASDAI scores decreased significantly in both the groups after therapy. A significant improvement in BASFI, patient pain VAS, patient global disease VAS, HAQ, and MCS of SF-36 was observed in both the groups. In the combination DMARD group, significant improvement in BASMI, FACIT and PCS of SF-36 and decrease in the serum MMP-3 levels was observed following...

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Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity

Abstract: Using several analytical approaches that have never been reported previously, we showed that MMP-3 is a more useful biomarker than ESR and CRP to detect high disease activity in AS.

Cited by 95 publications

References 27 publications

Serum matrix metalloproteinases-3 levels in patients with ankylosing spondylitis

Serum matrix metalloproteinases-3 levels in patients with ankylosing spondylitis

Histopathological changes in supraspinous ligaments, ligamentum flava and paraspinal muscle tissues of patients with ankylosing spondylitis

A Prospective Double Blind Placebo Controlled Trial of Combination Disease Modifying Antirheumatic Drugs vs. Monotherapy (Sulfasalazine) in Patients with Inflammatory Low Backache in Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy

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