کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10212248 | 1671350 | 2018 | 48 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Glucose dependent miR-451a expression contributes to parathyroid hormone mediated osteoblast differentiation
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کلمات کلیدی
pTH2-DOGstructural model indexscrambled siRNARunX-2OSR1Tb.NTb.SpSMIp27BMCsAMPKBMP-42-DeoxyglucoseOVXIGF-1BMDPI3KAICAR5-aminoimidazole-4-carboxamide ribonucleotideμCTMCOmTORBV/TV - BV / TVPhosphatidylinositol-4,5-bisphosphate 3-kinase - Phosphatidylinositol-4،5-bisphosphate 3-kinaseALP - آلکالن فسفاتازAlkaline phosphatase - آلکالین فسفاتاز یا فسفاتاز قلیاییbone morphogenetic protein-4 - استخوان مورفوژنیک پروتئین -4Insulin like growth factor-1 - انسولین مانند عامل رشد 1Ovariectomy - اوفورکتومی، تخمدان برداریOct-1 - اکتبر 1Bone mineral density - تراکم معدنی استخوانOsteoblast differentiation - تمایز استئوبلاستMicro-computed tomography - توموگرافی کامپیوتری میکروtrabecular separation - جداسازی ترابکولارBone marrow cells - سلول های مغز استخوانtrabecular number - شماره تراککالRunt-related transcription factor 2 - عامل رونویسی مرتبط با روت 2MicroRNA - میکرو RNA MiRNA - میکروRNA، ریزآرانای، miRNAmammalian target of rapamycin - هدف پستانداران رپامایسینparathyroid hormone - هورمون پاراتیروئید5′ adenosine monophosphate-activated protein kinase - پروتئین کیناز فعال شده با آدنوزین مونوفسفات 5 'Glucose - گلوکز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Parathyroid hormone (PTH; amino acid 1-34, known as teriparatide) has reported promoting differentiation and glucose uptake in osteoblasts. However, how PTH regulates glucose metabolism to facilitate osteoblast differentiation is not understood. Here, we report that PTH promotes glucose dependent miR-451a expression which stimulates osteoblast differentiation. In addition to glucose uptake, PTH suppresses AMPK phosphorylation via PI3K-mTOR-AKT axis thereby preventing phosphorylation and inactivation of octamer-binding transcription factor 1 (OCT-1) which has been reported to act on the promoter region of miR-451a. Modulation of AMPK activity controls miR-451a levels in differentiating osteoblasts. Moreover, pharmacological inhibition of PI3K-mTOR-AKT axis suppressed miR-451a via increased AMPK activity. We report that this glucose regulated miRNA is an anabolic target and transfection of miR-451a mimic induces osteoblast differentiation and mineralization in vitro. These actions were mediated through the suppression of Odd-skipped related 1 (Osr1) and activation of Runx2 transcription. When injected in vivo, the miR-451a mimic significantly increased osteoblastogenesis, mineralization, reversed ovariectomy induced bone loss and improved bone strength. Together, these findings suggest that enhanced osteoblast differentiation associated with bone formation in case of PTH therapy is also a consequence of elevated miR-451a levels via glucose regulation. Consequently, this miRNA has the potential to be a therapeutic target for conditions of bone loss.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 117, December 2018, Pages 98-115
Journal: Bone - Volume 117, December 2018, Pages 98-115
نویسندگان
Anirudha Karvande, Priyanka Kushwaha, Naseer Ahmad, Sulekha Adhikary, Priyanka Kothari, Ashish Kumar Tripathi, Vikram Khedgikar, Ritu Trivedi,