Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties

G Mabilleau, A Mieczkowska, Nigel Irwin, Y Simon Y, M Audran, Peter Flatt, D Chappard D

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone.
LanguageEnglish
Pages61-68
Number of pages8
JournalBone
Volume63
Early online date1 Mar 2014
DOIs
Publication statusPublished - 30 Jun 2014

Fingerprint

Bone and Bones
Glucose
Peptides
Hormones
Dipeptidyl Peptidase 4
X-Ray Microtomography
Bone Matrix
Bone Remodeling
Hardness
Therapeutic Uses
Microscopy
Collagen
Injections
Enzymes
Therapeutics

Keywords

  • N-AcGIP
  • Bone material properties
  • qBEI
  • Nanoindentation
  • Collagen maturity

Cite this

Mabilleau, G ; Mieczkowska, A ; Irwin, Nigel ; Simon Y, Y ; Audran, M ; Flatt, Peter ; Chappard D, D. / Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties. In: Bone. 2014 ; Vol. 63. pp. 61-68.
@article{aa7ad848939746ffbe874a62006d22c6,
title = "Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties",
abstract = "Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12{\%}), hardness (14{\%}), indentation modulus (13{\%}) and dissipated energy (16{\%}) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22{\%}) and collagen maturity (13{\%}) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone.",
keywords = "N-AcGIP, Bone material properties, qBEI, Nanoindentation, Collagen maturity",
author = "G Mabilleau and A Mieczkowska and Nigel Irwin and {Simon Y}, Y and M Audran and Peter Flatt and {Chappard D}, D",
year = "2014",
month = "6",
day = "30",
doi = "10.1016/j.bone.2014.02.013",
language = "English",
volume = "63",
pages = "61--68",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier",

}

Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties. / Mabilleau, G; Mieczkowska, A; Irwin, Nigel; Simon Y, Y; Audran, M; Flatt, Peter; Chappard D, D.

In: Bone, Vol. 63, 30.06.2014, p. 61-68.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties

AU - Mabilleau, G

AU - Mieczkowska, A

AU - Irwin, Nigel

AU - Simon Y, Y

AU - Audran, M

AU - Flatt, Peter

AU - Chappard D, D

PY - 2014/6/30

Y1 - 2014/6/30

N2 - Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone.

AB - Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone.

KW - N-AcGIP

KW - Bone material properties

KW - qBEI

KW - Nanoindentation

KW - Collagen maturity

UR - https://pure.ulster.ac.uk/en/publications/beneficial-effects-of-a-n-terminally-modified-gip-agonist-on-tiss-3

U2 - 10.1016/j.bone.2014.02.013

DO - 10.1016/j.bone.2014.02.013

M3 - Article

VL - 63

SP - 61

EP - 68

JO - Bone

T2 - Bone

JF - Bone

SN - 8756-3282

ER -