کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5889422 | 1568135 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The y6 receptor suppresses bone resorption and stimulates bone formation in mice via a suprachiasmatic nucleus relay
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
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چکیده انگلیسی
The neuropeptide Y system is known to play an important role in the regulation of bone homeostasis and while the functions of its major receptors, Y1R and Y2R, in this process have become clearer, the contributions of other Y-receptors, like the y6 receptor (y6R), are unknown. Y6R expression is restricted to the suprachiasmatic nucleus (SCN) of the hypothalamus, an area known to regulate circadian rhythms, and the testis. Here we show that lack of y6R signalling, results in significant reduction in bone mass, but no changes in bone length. Male and female y6R knockout (KO) mice display reduced cortical and cancellous bone volume in axial and appendicular bones. Mechanistically, the reduction in cancellous bone is the result of an uncoupling of bone remodelling, leading to an increase in osteoclast surface and number, and a reduction in osteoblast number, osteoid surface, mineralizing surface and bone formation rate. y6R KO mice displayed increased numbers of osteoclast precursors and produced greater numbers of osteoclasts in RANKL-treated cultures. They also produced fewer CFU-ALP osteoblast precursors in the marrow and showed reduced mineralization in primary osteoblastic cultures, as well as reduced expression for the osteoblast lineage marker, alkaline phosphatase, in bone isolates. The almost exclusive location of y6Rs in the hypothalamus suggests a critical role of central neuronal pathways controlling this uncoupling of bone remodelling which is in line with known actions or other Y-receptors in the brain. In conclusion, y6R signalling is required for maintenance of bone mass, with loss of y6R uncoupling bone remodelling and resulting in a negative bone balance. This study expands the scope of hypothalamic regulation of bone, highlighting the importance for neural/endocrine coordination and their marked effect upon skeletal homeostasis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 84, March 2016, Pages 139-147
Journal: Bone - Volume 84, March 2016, Pages 139-147
نویسندگان
Ee-Cheng Khor, Ernie Yulyaningsih, Frank Driessler, Natasha KovaÄiÄ, Natalie K.Y. Wee, Rishikesh N. Kulkarni, Nicola J. Lee, Ronaldo F. Enriquez, Jiake Xu, Lei Zhang, Herbert Herzog, Paul A. Baldock,