Publications (2)9.86 Total impact
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Article: Osteoprotegerin causes apoptosis of endothelial progenitor cells by induction of oxidative stress.
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ABSTRACT: OBJECTIVE: Elevated serum osteoprotegerin (OPG) represents an independent risk factor for atherosclerotic disease, although the underlying mechanism is not clear. Here, we investigated the association of serum OPG and circulating endothelial progenitor cells (EPCs) numbers, and explored the effect of OPG on EPCs apoptosis and its underlying mechanisms. METHODS: EPCs were enumerated in peripheral blood of 91 patients with systemic lupus erythematosus (SLE) using flow cytometry. Cultured EPCs, isolated from peripheral blood, were challenged with OPG and apoptosis was evaluated by TUNEL staining. Apoptosis related proteins were measured by quantitative real-time PCR (qPCR) and Western blot analysis. Reactive oxygen species (ROS) was detected by flow cytometry, and the expression of NADPH oxidase (Nox) and mitogen-activated protein kinases (MAPK) was measured by qPCR and Western blot analysis. RESULTS: Serum OPG level was independently associated with EPCs reduction in SLE patients. In vitro treatment of OPG significantly induced the apoptosis of EPCs. This effect was mediated by syndecan-4 on EPCs. OPG-induced apoptosis was abolished by ROS scavenger N-acetyl cysteine and Nox inhibitor diphenyleniodonium. OPG increased ROS production through activation of Nox2 and Nox4, and triggered phosphorylation of ERK1/2 and p38 MAPK. Quenching of ROS by knockdown of Nox2 or Nox4 transcripts inhibited phosphorylation of ERK1/2 and p38 MAPK. Moreover, inhibitors of ERK1/2 and p38 MAPK decreased ROS production and subsequent EPCs apoptosis, indicating a feed forward loop between Nox and MAPK to amplify ROS production related to apoptosis. CONCLUSION: Elevated OPG increases the apoptosis of EPCs by induction of oxidative stress. © 2013 American College of Rheumatology.Arthritis & Rheumatism 05/2013; · 7.87 Impact Factor -
Article: Serum leptin levels are associated with the presence of syndesmophytes in male patients with ankylosing spondylitis.
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ABSTRACT: The aim of this study is to clarify the association between serum leptin levels and the presence of syndesmophytes in male patients with ankylosing spondylitis (AS). Seventy-two male patients with AS and 20 age-matched healthy male controls were included. Patients were stratified by the presence of syndesmophytes. Serum leptin levels were measured and adjusted for body mass index (BMI). In addition, bone-specific alkaline phosphatase (BALP), osteocalcin, and telopeptide of type I collagen were determined. Patients with syndesmophytes were associated with older age (p < 0.001), longer disease duration (p = 0.003), and higher BMI (p = 0.038). Serum leptin levels and leptin per BMI (leptin/BMI) ratio were not different between AS patients and healthy controls. However, serum leptin/BMI ratio was significantly higher in patients with syndesmophytes compared to those without (p = 0.010). In multivariate analysis, higher serum leptin/BMI ratio remained significantly associated with the presence of syndesmophytes (p = 0.029). Moreover, serum leptin/BMI ratio was positively correlated with serum BALP (γ = 0.279, p = 0.039). However, there was no significant association between serum leptin/BMI ratio and bone mineral density. Serum leptin levels are elevated in male AS patients with syndesmophytes and were found to be correlated with bone formation marker, suggesting a potential role of leptin in new bone formation in AS.Clinical Rheumatology 05/2012; 31(8):1231-8. · 2.00 Impact Factor
