Abstract
| Language | English |
|---|---|
| Pages | 61-68 |
| Number of pages | 8 |
| Journal | Bone |
| Volume | 63 |
| Early online date | 1 Mar 2014 |
| DOIs | |
| Publication status | Published - 30 Jun 2014 |
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Keywords
- N-AcGIP
- Bone material properties
- qBEI
- Nanoindentation
- Collagen maturity
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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 journal › Article
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 -