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.
authors.affiliation: LUNAM Université, GEROM-LHEA, Institut de Biologie en Santé, Angers, France.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mieczkowska
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappard
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mabilleau
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011964:Receptors, Gastrointestinal Hormone / Q000172:deficiency* / Q000235:genetics; D017550:Spectroscopy, Fourier Transform Infrared; D055114:X-Ray Microtomography
chemical_list: D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor
keywords: Bone quality; Bone strength; GIP; GIPR; Gut hormone; Nanoindentation