Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality |
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| Affiliation: | 1. LUNAM Université, GEROM-LHEA, Institut de Biologie en Santé, Angers, France;2. School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom;1. Department of Biomedical Engineering, University of Southern California, Los Angeles CA, United States;2. Department of Mechanical and Industrial Engineering, Northeastern University, Boston MA, United States;3. Children''s Orthopaedic Center, Children''s Hospital Los Angeles, Los Angeles CA, United States;1. Clinical and Molecular Osteoporosis Research Unit, Dept. of Clinical Science Malmö, Lund University;2. Dept of Orthopaedics, Skåne University Hospital Malmö, Sweden;3. Dept of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;4. Dept of Clinical Sciences, Diabetes and Endocrinology, CRC, Lund University, Lund, Sweden;5. Steno Diabetes Center, Gentofte, Denmark;6. Medical Genetics Unit, Dept. of Clinical Sciences Malmö, Lund University, Sweden;1. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark;2. Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark;3. Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark |
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| 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. |
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