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Updated: Aug 14, 2026
Skeletal Muscle Gender Dimorphism from Proteomics
Published on: December 14, 2011
Sex-dependent divergence between skeletal and cardiac responses to phosphate load in experimental CKD
Lauriane Hivert1, Christophe Soulage2, Laurence Bessueille3
1INSERM UMR 1059 SAINBIOSE, Saint-Etienne, France.
Insights
Chronic kidney disease (CKD) causes mineral and bone disorders (MBD). High phosphate diets exacerbate MBD, particularly skeletal issues in female mice, highlighting sex-based differences in CKD progression.
Area of Science:
- Nephrology
- Endocrinology
- Skeletal Biology
Background:
- Chronic kidney disease (CKD) disrupts mineral homeostasis, leading to mineral and bone disorders (MBD).
- CKD affects women more frequently but men experience greater cardiovascular impact.
- Investigating sex differences in CKD-MBD is crucial for understanding disease progression.
Purpose of the Study:
- To characterize CKD-induced MBD in CD1 mice.
- To investigate potential sex differences in MBD development under normal and high phosphate conditions.
- To establish a sensitive mouse model for studying female-predominant skeletal vulnerability in CKD.
Main Methods:
- Male and female CD1 mice underwent 5/6 nephrectomy (Nx) to induce CKD.
- Mice were fed either a normal phosphate (NP) or high phosphate (HP) diet for 10 weeks.
- Markers of mineral metabolism, cardiac hypertrophy, and bone parameters were assessed.
Main Results:
- Nx mice exhibited elevated FGF23, PTH, and osteopontin, especially under HP diet.
- Fibroblast growth factor 23 (FGF23) increases were significantly higher in female mice.
- High phosphate diet induced cardiac hypertrophy in males and more severe bone disorders in females.
Conclusions:
- High phosphate diet exacerbates MBD in CKD mice, with distinct sex-specific phenotypes.
- Female CD1 mice show greater skeletal vulnerability, making them a suitable model for studying female-predominant bone issues in CKD.
- The phosphaturic effect of FGF23 remained sufficient to maintain stable phosphatemia in this early-stage CKD model.
Abstract:
Chronic kidney disease (CKD) induces a progressive decline in kidney function, leading to increased inorganic phosphate (Pi) load resulting in higher fibroblast growth factor 23 (FGF23) and cardiovascular complications including vascular calcifications (VC). Parallel rise of parathyroid hormone (PTH) increases bone resorption and release of calcium and Pi. These mineral and bone disorders (MBD) are central to the abnormalities observed in CKD. CKD has higher prevalence in women but higher cardiovascular impact on men, with increased risk of progressing to late stages. Here we characterize CKD-induced MBD in CD1 mice, and investigate sex differences. Twenty-week old male (M) and female (F) mice underwent 5/6 nephrectomy (Nx) then were fed either a normal (NP, 0.55% Pi) or a high phosphate diet (HP, 1.65% Pi) for 10 weeks. Nx mice showed increased markers of mineral metabolism, particularly under HP, including FGF23 (especially in F; HP vs NP: M +184%, F +770%), PTH (M +118%, F +201%) and osteopontin (M +92%, F +74%). Phosphatemia remained stable indicating that the phosphaturic effects of FGF23 were still sufficient, similar to early-stage CKD. Under HP cardiomyocyte hypertrophy was significant in M (+28% cardiomyocyte area vs NP) while bone disorders were more pronounced in F, with increased cortical porosity (+28% vs NP) and turnover. No VC was detected. Thus, HP diet induced a more severe mineral and bone phenotype in Nx CD1 female mice, making this strain a sensitive model to investigate female-predominant skeletal vulnerability in CKD.
