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Bone matrix quality in a developing high-fat diet mouse model is altered by RAGE deletion
Samuel J Stephen1, Stacyann Bailey1, Danielle N D'Erminio2
1Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute, Troy, NY, USA.
Bone
|June 19, 2022
Summary
Obesity in adolescents increases fracture risk by degrading bone quality through inflammation. Removing the Receptor for Advanced Glycation End products (RAGE) mitigated these negative effects, particularly in females.
Area of Science:
- Bone biology
- Metabolic disorders
- Inflammation
Background:
- Adolescent obesity is linked to chronic inflammation and increased fracture risk, challenging traditional views of bone protection by body mass.
- The Receptor for Advanced Glycation End products (RAGE) is an inflammatory regulator potentially affecting bone metabolism.
- The role of RAGE in skeletal fragility within the context of adolescent overweightness and obesity remains unclear.
Purpose of the Study:
- To investigate the impact of RAGE deficiency on skeletal fragility in adolescent mice subjected to a high-fat diet.
- To determine if low-grade inflammation, mediated by RAGE, contributes to bone quality deterioration and fracture risk in overweight adolescents.
- To analyze the multiscale structural, mechanical, and chemical properties of bone.
Main Methods:
- Micro-computed tomography (micro-CT) for structural analysis.
- Mechanical testing for bone strength and deformation.
- Raman spectroscopy and nanoindentation for material properties and chemical analysis.
- Comparison of wild-type (WT) and RAGE null (KO) mice fed low-fat (LF) or high-fat (HF) diets.
Main Results:
- Overweight WT mice on HF diet showed degraded mineral quality and increased matrix glycoxidation (pentosidine, carboxymethyl-lysine).
- HF diet in female mice led to reduced cortical surface expansion and bone mineral density, with increased material damage and plastic deformation compared to males.
- RAGE KO mitigated glycoxidative accumulation, preserved bone mineral quantity, and improved the elastic to hard (E/H) ratio in females.
Conclusions:
- Bone quality and function in overweight adolescents are complex, multi-scale, and sex-dependent.
- RAGE-controlled glycoxidation is a key factor in the deterioration of bone matrix quality and mechanical integrity.
- Targeting RAGE-mediated glycoxidation presents a potential strategy to preserve bone quality and reduce fracture risk in overweight adolescents.
