کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10903886 1086537 2015 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation - Description of a novel in vitro model
ترجمه فارسی عنوان
عوامل موثر در خون بیماران مبتلا به دیابت نوع 2 بر بلوغ استئوآباد تاثیر می گذارند - شرح یک مدل جدید در آزمایشگاهی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی
Type 2 diabetes mellitus (T2DM) is one of the most frequent metabolic disorders in industrialized countries. Among other complications, T2DM patients have an increased fracture risk and delayed fracture healing. We have demonstrated that supraphysiological glucose and insulin levels inhibit primary human osteoblasts׳ maturation. We aimed at developing a more physiologically relevant in vitro model to analyze T2DM-mediated osteoblast changes. Therefore, SCP-1-immortalized pre-osteoblasts were differentiated with T2DM or control (non-obese and obese) sera. Between both control groups, no significant changes were observed. Proliferation was significantly increased (1.69-fold), while AP activity and matrix mineralization was significantly reduced in the T2DM group. Expression levels of osteogenic marker genes and transcription factors were altered, e.g. down-regulation of RUNX2 and SP-7 or up-regulation of STAT1, in the T2DM group. Active TGF-β levels were significantly increased (1.46-fold) in T2DM patients׳ sera. SCP-1 cells treated with these sera showed significantly increased TGF-β signaling (2.47-fold). Signaling inhibition effectively restored osteoblast maturation in the T2DM group. Summarizing our data, SCP-1 cells differentiated in the presence of T2DM patients׳ serum exhibit reduced osteoblast function. Thus, this model has a high physiological impact, as it can identify circulating factors in T2DM patients׳ blood that may affect bone function, e.g. TGF-β.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 332, Issue 2, 15 March 2015, Pages 247-258
نویسندگان
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