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Updated: Feb 18, 2026
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Sclerostin deficiency modifies the development of CKD-MBD in mice
Nadine Kaesler1, Anja Verhulst2, Annelies De Maré2
1Department of Nephrology, University Hospital of the RWTH Aachen, Germany.
Abstract:
Sclerostin is a soluble antagonist of canonical Wnt signaling and a strong inhibitor of bone formation. We present experimental data on the role of sclerostin in chronic kidney disease - bone mineral disorder (CKD-MBD).
Methods:
We performed 5/6 nephrectomies in 36-week-old sclerostin-deficient (SOST-/-) B6-mice and in C57BL/6J wildtype (WT) mice. Animals received a high phosphate diet for 11weeks. The bones were analyzed by high-resolution micro-computed tomography (μCT) and quantitative bone histomorphometry. Aortic tissue was analyzed regarding the extent of vascular calcification.
Results:
All nephrectomized mice had severe renal failure, and parathyroid hormone was highly increased compared to corresponding sham animals. All SOST-/- animals revealed the expected high bone mass phenotype. Overall, the bone compartment in WT and SOST-/- mice responded similarly to nephrectomy. In uremic WT animals, μCT data at both the distal femur and lumbar spine revealed significantly increased trabecular volume compared to non-uremic WTs. In SOST-/- mice, the differences between trabecular bone volume were less pronounced when comparing uremic with sham animals. Cortical thickness and cortical bone density at the distal femur decreased significantly and comparably in both genotypes after 5/6 nephrectomy compared to sham animals (cortical bone density -18% and cortical thickness -32%). Overall, 5/6 nephrectomy and concomitant hyperparathyroidism led to a genotype-independent loss of cortical bone volume and density. Overt vascular calcification was not detectable in either of the genotypes.
Conclusion:
Renal osteodystrophy changes were more pronounced in WT mice than in SOST-/- mice. The high bone mass phenotype of sclerostin deficiency was detectable also in the setting of chronic renal failure with severe secondary hyperparathyroidism.
Insights
Sclerostin deficiency preserves bone mass in chronic kidney disease models, despite severe renal failure and hyperparathyroidism. Sclerostin inhibition may offer therapeutic benefits for CKD-MBD.
Area of Science:
- Nephrology
- Endocrinology
- Bone Biology
Background:
- Sclerostin inhibits bone formation by antagonizing Wnt signaling.
- Chronic kidney disease-mineral bone disorder (CKD-MBD) involves complex bone abnormalities.
- The role of sclerostin in CKD-MBD requires further elucidation.
Purpose of the Study:
- To investigate the impact of sclerostin deficiency on bone and vascular changes in a mouse model of CKD-MBD.
Main Methods:
- Sclerostin-deficient (SOST-/-) and wildtype (WT) mice underwent 5/6 nephrectomy or sham surgery.
- Mice were fed a high-phosphate diet for 11 weeks.
- Bone analysis used micro-computed tomography (μCT) and histomorphometry; aortic tissue assessed vascular calcification.
Main Results:
- Nephrectomized mice exhibited renal failure and elevated parathyroid hormone.
- SOST-/- mice maintained a high bone mass phenotype.
- Both genotypes showed similar genotype-independent cortical bone loss and density reduction post-nephrectomy.
- Vascular calcification was not detected in either genotype.
Conclusions:
- Sclerostin deficiency mitigates renal osteodystrophy in CKD-MBD.
- The high bone mass phenotype associated with sclerostin deficiency persists even with severe secondary hyperparathyroidism.
- These findings suggest sclerostin is a potential therapeutic target for CKD-MBD.
