ECTS Abstracts (2015) 1 P31

Glucose-dependent insulinotropic polypeptide is required for an optimal bone quality

Benoit Gobron1, Satoko Kuwahara2, Sheng Zhang3, Norio Harada2, Beatrice Bouvard4, Erick Legrand4, Burton Wice3, Nobuya Inagaki2, Daniel Chappard1 & Guillaume Mabilleau1


1LUNAM University, Angers, France; 2Kyoto University, Kyoto, Japan; 3Washington University, Saint Louis, Missouri, USA; 4University Hospital, Angers, France.


Background: Rapidly after meal ingestion, gut hormones are release in the blood stream and induce a response in target cells expressing the gut hormone receptor. Among them, a role for the glucose-dependent insulinotropic polypeptide receptor (GIPr) in controlling bone strength and quality has previously been reported. GIPr KO animals presented with higher trabecular bone mass and reduction in cortical thickness. Nevertheless the tissue mineral density and the extent of collagen cross-linking were dramatically altered in trabecular and cortical bone. However, a second animal model of GIPr deletion exists and the opposite phenotype has been reported in this experimental model. The aims of the present study were to decipher the role of GIP in bone physiology by using an animal model of GIP deletion (GIP-GFP KI) or animals deprived in GIP-producing cells (GIP-DT).

Methods: Eight GIP-GFP KI and GIP-DT mice (16-week old) were age- and sex-matched with eight wild-type (WT) littermates. Trabecular and cortical bone microarchitecture were studied by high resolution microCT at the femurs and tibias. Bone strength was investigated by three-point bending. Non-parametric Mann-Whitney U-test was used to compare differences between groups.

Results: As compared with control mice, GIP-GFP KI animals exhibited significant reductions in BV/TV (22%, p<0.001), trabecular number (19%, p<0.001) and higher value for trabecular separation (14%, p=0.007). Surprisingly, these modifications of trabecular microarchitecture were not seen in GIP-DT animals, lacking GIP but also any other gut hormones made by K cells. Investigation of cortical microarchitecture revealed a significant reduction in cortical thickness in GIP-GFP KI mice (16%, p=0.005) whilst the same parameter was reduced in GIP-DT animals without reaching statistical significance. Furthermore, bone strength assessed by 3-point bending highlighted reduction in stiffness almost significant in GIP-GFP KI mice (10%, p=0.07) but not in GIP-DT animals (p=0.28).

Conclusions: These results support a role for the GIP/GIPr pathway in controlling bone strength and quality. However, these data also suggest that GIP-DT animal have a compensatory mechanism to maintain bone quality in the absence of GIP.

Disclosure: The authors declared no competing interests.

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