کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5888802 | 1568129 | 2016 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Disruption of biomineralization pathways in spinal tissues of a mouse model of diffuse idiopathic skeletal hyperostosis
ترجمه فارسی عنوان
اختلال در مسیرهای بیومینالالیزاسیون در بافت های نخاعی یک مدل موش از هیپرتومیز اسکلتی منتشر ای دیوپاتیک
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کلمات کلیدی
ENT1Alkaline phosphatase - آلکالین فسفاتاز یا فسفاتاز قلیاییEquilibrative nucleoside transporter 1 - حمل کننده نوکلئوز تعادل 1Intervertebral disc - دیسک بین مهرهایDISH - ظرفAnnulus fibrosus - فیبروروز انولوسMineralization - معدنی سازی یا کانی سازیDiffuse idiopathic skeletal hyperostosis - هیپرتروزی اسکلتی ایدیوپاتیک دیافراگم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
چکیده انگلیسی
Equilibrative nucleoside transporter 1 (ENT1) mediates passage of adenosine across the plasma membrane. We reported previously that mice lacking ENT1 (ENT1â/â) exhibit progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Here, we investigated mechanisms underlying aberrant mineralization in ENT1â/â mice. Micro-CT revealed ectopic mineralization of spinal tissues in both male and female ENT1â/â mice, involving the annulus fibrosus of the intervertebral discs (IVDs) of older mice. IVDs were isolated from wild-type and ENT1â/â mice at 2Â months of age (prior to disc mineralization), 4, and 6Â months of age (disc mineralization present) and processed for real-time PCR, cell isolation, or histology. Relative to the expression of ENTs in other tissues, ENT1 was the primary nucleoside transporter expressed in wild-type IVDs and mediated the functional uptake of [3H]2-chloroadenosine by annulus fibrosus cells. No differences in candidate gene expression were detected in IVDs from ENT1â/â and wild-type mice at 2 or 4Â months of age. However, at 6Â months of age, expression of genes that inhibit biomineralization Mgp, Enpp1, Ank, and Spp1 were reduced in IVDs from ENT1â/â mice. To assess whether changes detected in ENT1â/â mice were cell autonomous, annulus fibrosus cell cultures were established. Compared to wild-type cells, cells isolated from ENT1â/â IVDs at 2 or 6Â months of age demonstrated greater activity of alkaline phosphatase, a promoter of biomineralization. Cells from 2-month-old ENT1â/â mice also showed greater mineralization than wild-type. Interestingly, altered localization of alkaline phosphatase activity was detected in the inner annulus fibrosus of ENT1â/â mice in vivo. Alkaline phosphatase activity, together with the marked reduction in mineralization inhibitors, is consistent with the mineralization of IVDs seen in ENT1â/â mice at older ages. These findings establish that both cell-autonomous and systemic mechanisms contribute to ectopic mineralization in ENT1â/â mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 90, September 2016, Pages 37-49
Journal: Bone - Volume 90, September 2016, Pages 37-49
نویسندگان
Hisataka Ii, Sumeeta Warraich, Neil Tenn, Diana Quinonez, David W. Holdsworth, James R. Hammond, S. Jeffrey Dixon, Cheryle A. Séguin,