کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10753763 1050345 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Premature chondrocyte apoptosis and compensatory upregulation of chondroregulatory protein expression in the growth plate of Goto-Kakizaki diabetic rats
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Premature chondrocyte apoptosis and compensatory upregulation of chondroregulatory protein expression in the growth plate of Goto-Kakizaki diabetic rats
چکیده انگلیسی
Type 2 diabetes mellitus (T2DM) is much more detrimental to bone than previously thought. Specifically, it is associated with aberrant bone remodeling, defective bone microstructure, poor bone quality, and growth retardation. The T2DM-associated impairment of bone elongation may result from a decrease in growth plate function, but the detailed mechanism has been unknown. The present study, therefore, aimed to test hypothesis that T2DM led to premature apoptosis of growth plate chondrocytes in Goto-Kakizaki (GK) type 2 diabetic rats, and thus triggered the compensatory responses to overcome this premature apoptosis, such as overexpression of Runt-related transcription factor (Runx)-2 and vascular endothelial growth factor (VEGF), the essential mediators for bone elongation. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) of epiphyseal sections successfully revealed increases in chondrocyte apoptosis in the hypertrophic zone (HZ) and chondro-osseous junction of GK rats. Quantitative immunohistochemical analysis further confirmed the overexpression of parathyroid hormone-related protein (PTHrP), Runx2 and VEGF, but not Indian hedgehog (Ihh) in the HZ. Analysis of blood chemistry indicated suppression of bone remodeling with a marked decrease in parathyroid hormone level. In conclusion, GK rats manifested a premature increase in chondrocyte apoptosis in the HZ of growth plate, and a compensatory overexpression of chondroregulatory proteins, such as PTHrP, Runx2, and VEGF. Our results, therefore, help explain how T2DM leads to impaired bone elongation and growth retardation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 452, Issue 3, 26 September 2014, Pages 395-401
نویسندگان
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