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

Maria Ellegaard; Cansu Agca; Solveig Petersen; Ankita Agrawal; Lars Schack Kruse; Ning Wang; Alison Gartland; Jens-Erik Beck Jensen; Niklas Rye Jørgensen; Yuksel Agca

doi:10.1007/s11302-017-9582-3

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

Maria Ellegaard, Cansu Agca, Solveig Petersen, Ankita Agrawal, Lars Schack Kruse, Ning Wang, Alison Gartland, Jens-Erik Beck Jensen, Niklas Rye Jørgensen, Yuksel Agca

Department of Clinical Medicine

5 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Purinergic Signalling
Volume	13
Issue number	4
Pages (from-to)	545-557
ISSN	1573-9538
DOIs	https://doi.org/10.1007/s11302-017-9582-3
Publication status	Published - 1 Dec 2017

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title = "Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor",

abstract = "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.",

author = "Maria Ellegaard and Cansu Agca and Solveig Petersen and Ankita Agrawal and Kruse, {Lars Schack} and Ning Wang and Alison Gartland and Jensen, {Jens-Erik Beck} and J{\o}rgensen, {Niklas Rye} and Yuksel Agca",

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T1 - Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor

AU - Ellegaard, Maria

AU - Agca, Cansu

AU - Petersen, Solveig

AU - Agrawal, Ankita

AU - Kruse, Lars Schack

AU - Wang, Ning

AU - Gartland, Alison

AU - Jensen, Jens-Erik Beck

AU - Jørgensen, Niklas Rye

AU - Agca, Yuksel

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

U2 - 10.1007/s11302-017-9582-3

DO - 10.1007/s11302-017-9582-3

M3 - Journal article

C2 - 28828576

SN - 1573-9538

VL - 13

SP - 545

EP - 557

JO - Purinergic Signalling

JF - Purinergic Signalling

IS - 4

ER -

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

Abstract

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