title: Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice.
abstract: A role for the gastro-intestinal tract in controlling bone remodeling is suspected since serum levels of bone remodeling markers are affected rapidly after a meal. Glucose-dependent insulinotropic polypeptide (GIP) represents a suitable candidate in mediating this effect. The aim of the present study was to investigate the effect of total inhibition of GIP signaling on trabecular bone volume, microarchitecture and quality. We used GIP receptor (GIPR) knockout mice and investigated trabecular bone volume and microarchitecture by microCT and histomorphometry. GIPR-deficient animals at 16 weeks of age presented with a significant (20%) increase in trabecular bone mass accompanied by an increase (17%) in trabecular number. In addition, the number of osteoclasts and bone formation rate was significantly reduced and augmented, respectively in these animals when compared with wild-type littermates. These modifications of trabecular bone microarchitecture are linked to a remodeling in the expression pattern of adipokines in the GIPR-deficient mice. On the other hand, despite significant enhancement in bone volume, intrinsic mechanical properties of the bone matrix was reduced as well as the distribution of bone mineral density and the ratio of mature/immature collagen cross-links. Taken together, these results indicate an increase in trabecular bone volume in GIPR KO animals associated with a reduction in bone quality.
authors.affiliation: LUNAM Université, GEROM-LHEA, Institut de Biologie en Santé, Angers, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Gaudin-Audrain
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.forename: Sity
authors.initials: S
authors.lastname: Mansur
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
authors.forename: Michel
authors.initials: M
authors.lastname: Baslé
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappard
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mabilleau
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002454:Cell Differentiation; D005260:Female; D005947:Glucose / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D010010:Osteoclasts / Q000166:cytology; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000502:physiology*; D017550:Spectroscopy, Fourier Transform Infrared; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D054392:Adipokines; D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor; D005947:Glucose