title: Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor.
abstract: Bone is permanently remodeled by a complex network of local, hormonal, and neuronal factors that affect osteoclast and osteoblast biology. Among these factors, a role for gastrointestinal hormones has been proposed based on the evidence that bone resorption dramatically falls after a meal. Glucagon-like peptide-1 (GLP1) is one of these gut hormones, and despite several reports suggesting an anabolic effect of GLP1, or its stable analogs, on bone mass, little is known about the effects of GLP1/GLP1 receptor on bone strength. In this study, we investigated by three-point bending, quantitative X-ray microradiography, microcomputed tomography, qBEI, and FTIRI bone strength and bone quality in male Glp1r knockout (Glp1r KO) mice when compared with control WT animals. Animals with a deletion of Glp1r presented with a significant reduction in ultimate load, yield load, stiffness, and total absorbed and post-yield energies when compared with WT animals. Furthermore, cortical thickness and bone outer diameter were significantly decreased in deficient animals. The mineral quantity and quality were not significantly different between Glp1r KO and WT animals. On the other hand, the maturity of the collagen matrix was significantly reduced in deficient animals and associated with lowered material properties. Taken together, these data support a positive effect of GLP1R on bone strength and quality.
authors.affiliation: Groupe d'Etudes sur le Remodelage Osseux et les bioMatériaux (GEROM)-LHEA, Service Commun d'Imageries et d'Analyses Microscopiques (SCIAM), IRIS-IBS Institut de Biologie en Santé, LUNAM Université, CHU d'Angers, 49933 Angers Cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mabilleau
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
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology*; D003094:Collagen / Q000502:physiology; D000067757:Glucagon-Like Peptide-1 Receptor; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018027:Receptors, Glucagon / Q000172:deficiency* / Q000235:genetics; D055114:X-Ray Microtomography
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D003094:Collagen
keywords: bone matrix; bone mineral; bone quality; bone strength; glucagon-like peptide-1