Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor

被引:0
作者
Maria Ellegaard
Cansu Agca
Solveig Petersen
Ankita Agrawal
Lars Schack Kruse
Ning Wang
Alison Gartland
Jens-Erik Beck Jensen
Niklas Rye Jørgensen
Yuksel Agca
机构
[1] Rigshospitalet,Department of Clinical Biochemistry
[2] University of Missouri,College of Veterinary Medicine
[3] University of Sheffield,Mellanby Centre for Bone Research
[4] Copenhagen University Hospital Hvidovre,Osteoporosis and Bone Metabolic Unit, Department of Endocrinology
[5] University of Southern Denmark,OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research
来源
Purinergic Signalling | 2017年 / 13卷
关键词
Genetic animal models; Osteoblasts; Osteoclasts; Cell/tissue signaling; P2Y2 purinergic receptors;
D O I
暂无
中图分类号
学科分类号
摘要
It is now widely recognized that purinergic signaling plays an important role in the regulation of bone remodeling. One receptor subtype, which has been suggested to be involved in this regulation, is the P2Y2 receptor (P2Y2R). In the present study, we investigated the effect of P2Y2R overexpression on bone status and bone cell function using a transgenic rat. Three-month-old female transgenic Sprague Dawley rats overexpressing P2Y2R (P2Y2R-Tg) showed higher bone strength of the femoral neck. Histomorphometry showed increase in resorptive surfaces and reduction in mineralizing surfaces. Both mineral apposition rate and thickness of the endocortical osteoid layer were higher in the P2Y2R-Tg rats. μCT analysis showed reduced trabecular thickness and structural model index in P2Y2R-Tg rats. Femoral length was increased in the P2Y2R-Tg rats compared to Wt rats. In vitro, there was an increased formation of osteoclasts, but no change in total resorption in cultures from P2Y2R-Tg rats. The formation of mineralized nodules was significantly reduced in the osteoblastic cultures from P2Y2R-Tg rats. In conclusion, our study suggests that P2Y2R is involved in regulation of bone turnover, due to the effects on both osteoblasts and osteoclasts and that these effects might be relevant in the regulation of bone growth.
引用
收藏
页码:545 / 557
页数:12
相关论文
共 141 条
[1]  
Ralevic V(1998)Receptors for purines and pyrimidines Pharmacol Rev 50 413-492
[2]  
Burnstock G(2013)Purinergic signalling in the musculoskeletal system Purinergic Signal 9 541-572
[3]  
Burnstock G(2001)P2X and P2Y purinoreceptors mediate ATP-evoked calcium signalling in optic nerve glia in situ Cell Calcium 30 251-259
[4]  
Arnett TR(1999)Signaling in human osteoblasts by extracellular nucleotides. Their weak induction of the c-fos proto-oncogene via Ca2+ mobilization is strongly potentiated by a parathyroid hormone/cAMP-dependent protein kinase pathway independently of mitogen-activated protein kinase J Biol Chem 274 14315-14324
[5]  
Orriss IR(1992)Evidence for P2-purinoceptors on human osteoblast-like cells J Bone Miner Res 7 485-491
[6]  
James G(2006)Osteoblast responses to nucleotides increase during differentiation Bone 39 300-309
[7]  
Butt AM(2007)Extracellular nucleotides block bone mineralization in vitro: evidence for dual inhibitory mechanisms involving both P2Y2 receptors and pyrophosphate Endocrinology 148 4208-4216
[8]  
Bowler WB(2013)ATP and UTP stimulate bone morphogenetic protein-2,-4 and -5 gene expression and mineralization by rat primary osteoblasts involving PI3K/AKT pathway Exp Cell Res 319 2028-2036
[9]  
Dixon CJ(1998)P2Y2 receptors are expressed by human osteoclasts of giant cell tumor but do not mediate ATP-induced bone resorption Bone 22 195-200
[10]  
Halleux C(1997)ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells J Cell Biol 139 497-506