title: Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice.
abstract: Low circulating IGF-I is associated with increased fracture risk. Conditional depletion of IGF-I produced in osteoblasts or osteocytes inhibits the bone anabolic effect of mechanical loading. Here, we determined the role of endocrine IGF-I for the osteogenic response to mechanical loading in young adult and old female mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by ≈70%) and control mice. The right tibia was subjected to short periods of axial cyclic compressive loading three times/wk for 2 wk, and measurements were performed using microcomputed tomography and mechanical testing by three-point bending. In the nonloaded left tibia, the LI-IGF-I(-/-) mice had lower cortical bone area and increased cortical porosity, resulting in reduced bone mechanical strength compared with the controls. Mechanical loading induced a similar response in LI-IGF-I(-/-) and control mice in terms of cortical bone area and trabecular bone volume fraction. In fact, mechanical loading produced a more marked increase in cortical bone mechanical strength, which was associated with a less marked increase in cortical porosity, in the LI-IGF-I(-/-) mice compared with the control mice. In conclusion, liver-derived IGF-I regulates cortical bone mass, cortical porosity, and mechanical strength under normal (nonloaded) conditions. However, despite an ∼70% reduction in circulating IGF-I, the osteogenic response to mechanical loading was not attenuated in the LI-IGF-I(-/-) mice.
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; johan.svensson@medic.gu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; School of Veterinary Sciences, Bristol United Kingdom;
authors.forename: Sara H
authors.initials: SH
authors.lastname: Windahl
authors.affiliation: The Royal Veterinary College, London United Kingdom; and.
authors.forename: Leanne
authors.initials: L
authors.lastname: Saxon
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;
authors.forename: Klara
authors.initials: K
authors.lastname: Sjögren
authors.affiliation: Department of Anatomy and Cell Biology, Institute of Cancer Research and Translational Medicine, Medical Research Center, University of Oulu, Oulu, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Koskela
authors.affiliation: Department of Anatomy and Cell Biology, Institute of Cancer Research and Translational Medicine, Medical Research Center, University of Oulu, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Tuukkanen
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D015519:Bone Density / Q000235:genetics; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology; D000071538:Cortical Bone / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000502:physiology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010012:Osteogenesis / Q000235:genetics*; D016062:Porosity; D013314:Stress, Mechanical; D013977:Tibia / Q000000981:diagnostic imaging / Q000378:metabolism*; D016474:Weight-Bearing; D055114:X-Ray Microtomography
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I
keywords: cortical bone mass; cortical porosity; insulin-like growth factor-I; liver-derived; mechanical loading