کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5585402 | 1568122 | 2017 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of endoplasmic reticulum stress in disuse osteoporosis
ترجمه فارسی عنوان
نقش استرس تناسلی اندوپلاسمی در پوکی استخوان
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کلمات کلیدی
SalubrinalM-CSFATF4eIF2αTRAPRANKLC/EBP homologous protein - C / EBP پروتئین همولوگALP - آلکالن فسفاتازAlkaline phosphatase - آلکالین فسفاتاز یا فسفاتاز قلیاییEndoplasmic reticulum stress - استرس شبکه آندوپلاسمیTartrate resistant acid phosphatase - اسید فسفاتاز مقاوم در برابر تتراتHindlimb unloading - تخلیه اسلحهeukaryotic translation initiation factor 2 alpha - ترجمه عامل ترجمه یوکاریوتی 2 عامل آلفاCHOP - تکه کردنDisuse - رد کردنendoplasmic reticulum - شبکه آندوپلاسمی eukaryotic translation initiation factor 2α - عامل آغازگر ترجمه یوکاریوتی 2αactivating transcription factor 4 - فعال کردن عامل رونویسی 4macrophage-colony stimulating factor - ماکروفاژ - کلنی عامل تحریک کنندهOsteoporosis - پوکی استخوانreceptor activator of nuclear factor kappa-B ligand - گیرنده گیرنده لیگاند کاپا-B فاکتور هسته ای
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
چکیده انگلیسی
Osteoporosis is a major skeletal disease with low bone mineral density, which leads to an increased risk of bone fracture. Salubrinal is a synthetic chemical that inhibits dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) in response to endoplasmic reticulum (ER) stress. To understand possible linkage of osteoporosis to ER stress, we employed an unloading mouse model and examined the effects of salubrinal in the pathogenesis of disuse osteoporosis. The results presented several lines of evidence that osteoclastogenesis in the development of osteoporosis was associated with ER stress, and salubrinal suppressed unloading-induced bone loss. Compared to the age-matched control, unloaded mice reduced the trabecular bone area/total area (B.Ar/T.Ar) as well as the number of osteoblasts, and they increased the osteoclasts number on the trabecular bone surface in a time-dependent way. Unloading-induced disuse osteoporosis significantly increased the expression of Bip, p-eIF2α and ATF4 in short-term within 6 h of tail suspension, but time-dependent decreased in HU2d to HU14d. Furthermore, a significant correlation of ER stress with the differentiation of osteoblasts and osteoclasts was observed. Administration of salubrinal suppressed the unloading-induced decrease in bone mineral density, B.Ar/T.Ar and mature osteoclast formation. Salubrinal also increased the colony-forming unit-fibroblasts and colony-forming unit-osteoblasts. It reduced the formation of mature osteoclasts, suppressed their migration and adhesion, and increased the expression of Bip, p-eIF2α and ATF4. Electron microscopy showed that rough endoplasmic reticulum expansion and a decreased number of ribosomes on ER membrane were observed in osteoblast of unloading mice, and the abnormal ER expansion was significantly improved by salubrinal treatment. A TUNEL assay together with CCAAT/enhancer binding protein homologous protein (CHOP) expression indicated that ER stress-induced osteoblast apoptosis was rescued by salubrinal. Collectively, the results support the notion that ER stress plays a key role in the pathogenesis of disuse osteoporosis, and salubrinal attenuates unloading-induced bone loss by altering proliferation and differentiation of osteoblasts and osteoclasts via eIF2α signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 97, April 2017, Pages 2-14
Journal: Bone - Volume 97, April 2017, Pages 2-14
نویسندگان
Jie Li, Shuang Yang, Xinle Li, Daquan Liu, Zhaonan Wang, Jialu Guo, Nian Tan, Zhe Gao, Xiaoyu Zhao, Jiuguo Zhang, Fanglin Gou, Hiroki Yokota, Ping Zhang,