Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality

A Mieczkowska, Nigel Irwin, Peter Flatt, D Chappard, G Mabilleau

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent insulinotropic polypeptide receptor (GIPR), is expressed in bone. In the present study we investigated bone strength and quality by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIR in a GIPR knockout (GIPR KO) mouse model and compared with control wild-type (WT) animals. Animals with a deletion of the GIPR presented with a significant reduction in ultimate load (-11%), stiffness (-16%), total absorbed (-28%) and post-yield energies (-27%) as compared with WT animals. Furthermore, despite no change in bone outer diameter, the bone marrow diameter was significantly increased and as a result cortical thickness was significantly decreased by 20% in GIPR deficient animals. Bone resorption at the endosteal surface was significantly increased whilst bone formation was unchanged in GIPR deficient animals. Deficient animals also presented with a pronounced reduction in the degree of mineralization of bone matrix. Furthermore, the amount of mature cross-links of collagen matrix was significantly reduced in GIPR deficient animals and was associated with lowered intrinsic material properties. Taken together, these data support a positive effect of the GIPR on bone strength and quality.
LanguageEnglish
Pages337-342
JournalBone
Volume56
Issue number2
DOIs
Publication statusPublished - 10 Jun 2013

Fingerprint

Bone and Bones
Wild Animals
Bone Resorption
Microradiography
Gastrointestinal Hormones
X-Ray Microtomography
Bone Matrix
Osteoclasts
Fourier Transform Infrared Spectroscopy
gastric inhibitory polypeptide receptor
Osteoblasts
Osteogenesis
Knockout Mice
Meals
Collagen
Bone Marrow
X-Rays
Hormones
Glucose
Peptides

Cite this

@article{332859d4d7a348028dfc0075ca5e7bb0,
title = "Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality",
abstract = "Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent insulinotropic polypeptide receptor (GIPR), is expressed in bone. In the present study we investigated bone strength and quality by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIR in a GIPR knockout (GIPR KO) mouse model and compared with control wild-type (WT) animals. Animals with a deletion of the GIPR presented with a significant reduction in ultimate load (-11{\%}), stiffness (-16{\%}), total absorbed (-28{\%}) and post-yield energies (-27{\%}) as compared with WT animals. Furthermore, despite no change in bone outer diameter, the bone marrow diameter was significantly increased and as a result cortical thickness was significantly decreased by 20{\%} in GIPR deficient animals. Bone resorption at the endosteal surface was significantly increased whilst bone formation was unchanged in GIPR deficient animals. Deficient animals also presented with a pronounced reduction in the degree of mineralization of bone matrix. Furthermore, the amount of mature cross-links of collagen matrix was significantly reduced in GIPR deficient animals and was associated with lowered intrinsic material properties. Taken together, these data support a positive effect of the GIPR on bone strength and quality.",
author = "A Mieczkowska and Nigel Irwin and Peter Flatt and D Chappard and G Mabilleau",
year = "2013",
month = "6",
day = "10",
doi = "10.1016/j.bone.2013.07.003",
language = "English",
volume = "56",
pages = "337--342",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier",
number = "2",

}

Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality. / Mieczkowska, A; Irwin, Nigel; Flatt, Peter; Chappard, D; Mabilleau, G.

In: Bone, Vol. 56, No. 2, 10.06.2013, p. 337-342.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality

AU - Mieczkowska, A

AU - Irwin, Nigel

AU - Flatt, Peter

AU - Chappard, D

AU - Mabilleau, G

PY - 2013/6/10

Y1 - 2013/6/10

N2 - Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent insulinotropic polypeptide receptor (GIPR), is expressed in bone. In the present study we investigated bone strength and quality by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIR in a GIPR knockout (GIPR KO) mouse model and compared with control wild-type (WT) animals. Animals with a deletion of the GIPR presented with a significant reduction in ultimate load (-11%), stiffness (-16%), total absorbed (-28%) and post-yield energies (-27%) as compared with WT animals. Furthermore, despite no change in bone outer diameter, the bone marrow diameter was significantly increased and as a result cortical thickness was significantly decreased by 20% in GIPR deficient animals. Bone resorption at the endosteal surface was significantly increased whilst bone formation was unchanged in GIPR deficient animals. Deficient animals also presented with a pronounced reduction in the degree of mineralization of bone matrix. Furthermore, the amount of mature cross-links of collagen matrix was significantly reduced in GIPR deficient animals and was associated with lowered intrinsic material properties. Taken together, these data support a positive effect of the GIPR on bone strength and quality.

AB - Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent insulinotropic polypeptide receptor (GIPR), is expressed in bone. In the present study we investigated bone strength and quality by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIR in a GIPR knockout (GIPR KO) mouse model and compared with control wild-type (WT) animals. Animals with a deletion of the GIPR presented with a significant reduction in ultimate load (-11%), stiffness (-16%), total absorbed (-28%) and post-yield energies (-27%) as compared with WT animals. Furthermore, despite no change in bone outer diameter, the bone marrow diameter was significantly increased and as a result cortical thickness was significantly decreased by 20% in GIPR deficient animals. Bone resorption at the endosteal surface was significantly increased whilst bone formation was unchanged in GIPR deficient animals. Deficient animals also presented with a pronounced reduction in the degree of mineralization of bone matrix. Furthermore, the amount of mature cross-links of collagen matrix was significantly reduced in GIPR deficient animals and was associated with lowered intrinsic material properties. Taken together, these data support a positive effect of the GIPR on bone strength and quality.

U2 - 10.1016/j.bone.2013.07.003

DO - 10.1016/j.bone.2013.07.003

M3 - Article

VL - 56

SP - 337

EP - 342

JO - Bone

T2 - Bone

JF - Bone

SN - 8756-3282

IS - 2

ER -