کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8625108 | 1568111 | 2018 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Age-related regulation of bone formation by the sympathetic cannabinoid CB1 receptor
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کلمات کلیدی
dopamine-β-hydroxylaseTb.Narachidonoyl ethanolamideTb.Thβ2AReCBsBFRCB22-arachidonoylglycerolCB12-AGMARcannabinoid-1Conn.DDBHAEABV/TV - BV / TVendocannabinoids - اندوکانبایوئید هاconnectivity density - تراکم اتصالCNS - دستگاه عصبی مرکزیcentral nervous system - سیستم عصبی مرکزیtrabecular number - شماره تراککالtrabecular thickness - ضخامت تراککالbone formation rate - میزان تشکیل استخوانnorepinephrine - نوراپی نفرین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The endocannabinoid (eCB) system, including its receptors, ligands, and their metabolizing enzymes, plays an important role in bone physiology. Skeletal cannabinoid type 1 (CB1) receptor signaling transmits retrograde signals that restrain norepinephrine (NE) release, thus transiently stimulating bone formation following an acute challenge, suggesting a feedback circuit between sympathetic nerve terminals and osteoblasts. To assess the effect of chronic in vivo occurrence of this circuit, we characterized the skeletal phenotype of mice with a conditional deletion of the CB1 receptor in adrenergic/noradrenergic cells, including sympathetic nerves. Whereas the deletion of the CB1 receptor did not affect bone mass accrual in the distal femoral metaphysis and in vertebral bodies of young, 12-week-old mice, it substantially increased bone mass in aged, 35-week-old mutant mice as compared to wild-type controls. Contrary to our expectations, specific deficiency of the CB1 receptor in sympathetic neurons led to a markedly increased bone mass phenotype, associated with an enhanced bone formation rate and reduced osteoclastogenesis. Mechanistically, the reduced skeletal eCB 'tone' in the null mice did not reflect in increased sympathetic tone and reduced bone formation, suggesting that constitutive genetic inactivation of sympathetic CB1 receptor disrupts the negative feedback loop between eCBs and NE signaling in bone.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 108, March 2018, Pages 34-42
Journal: Bone - Volume 108, March 2018, Pages 34-42
نویسندگان
Saif Deis, Raj Kamal Srivastava, Inigo Ruiz de Azua, Laura Bindila, Saja Baraghithy, Beat Lutz, Itai Bab, Joseph Tam,