کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5669288 1407955 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanical force-mediated pathological cartilage thinning is regulated by necroptosis and apoptosis
ترجمه فارسی عنوان
نازک شدن غضروف آسیب دیده توسط مکانیزم نیروی مکانیکی توسط نروپتوز و آپوپتوز تنظیم می شود
کلمات کلیدی
غضروف ماندوبولار، کندروسیت مندیبول، نئروپوتوزیس آپوپتوز نیروی مکانیکی فشرده،
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی ایمونولوژی، آلرژی و روماتولوژی
چکیده انگلیسی

SummaryObjectiveThis study aimed to identify the mechanisms underlying mandibular chondrocyte cell death and cartilage thinning in response to mechanical force.Material and methodsAn in vivo model (compressive mechanical force) and an in vitro model (TNF-α+cycloheximide) were used to induce mandibular chondrocyte necroptosis. Hematoxylin and eosin staining and transmission electron microscopy were used to assess histological and subcellular changes in mandibular chondrocyte. Immunohistochemistry, western blotting, and real-time PCR were performed to evaluate changes in necroptotic protein markers. Cell activity, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were examined in vitro.ResultsThe expression of RIP1, RIP3 and Caspase-8 in mandibular chondrocytes significantly increased after 4 days of compressive mechanical force. Furthermore, the inhibition of necroptosis by Necrostatin-1 (Nec-1) or the inhibition of apoptosis by N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD) partially restored mechanical force-mediated mandibular cartilage thinning and chondrocyte death. Moreover, a synergistic effect on cell death inhibition and mandibular cartilage thickness restoration were found when treated with Nec-1+Z-VAD. The results of the in vitro model were in line with the in vivo ones, indicating that the changes in MMP and ROS generation contributed to mandibular chondrocyte apoptosis and necroptosis.ConclusionIn addition to apoptosis, necroptosis also plays critical roles in pathological changes in mandibular cartilage after compressive mechanical force stimulation, implying RIP1, a master protein that mediates both necroptosis and apoptosis, as a potential therapeutic target in temporal mandibular osteoarthritis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Osteoarthritis and Cartilage - Volume 25, Issue 8, August 2017, Pages 1324-1334
نویسندگان
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