Roxadustat ameliorates bone microarchitectural deterioration in CKD-MBD rats in association with mitigated systemic micro-inflammation and restored FGF23–Wnt/β-catenin signaling
7 affiliations
- 1Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University
- 2Clinical Research Center for Chronic Kidney Disease in Qinghai Province
- 3Qinghai University
- 4Department of Public Health, Medical College, Qinghai University
- 5Department of Nephrology, The Affiliated Hospital of Qinghai University
- 6Department of Nephrology, Beijing Hospital
- 7Department of Geriatrics, The Affiliated Hospital of Qinghai University
Abstract
Elevated FGF23 is associated with bone microarchitectural deterioration in chronic kidney dis-ease-mineral and bone disorder (CKD-MBD). While roxadustat (a HIF-PHI) is established for the treatment of renal anemia, its potential bone-protective effects in CKD-MBD remain unclear. We investigated whether roxadustat ameliorates femoral microarchitectural deterioration in CKD-MBD rats in association with FGF23 downregulation and restoration of Wnt/β-catenin signaling. A CKD-MBD rat model was established by unilateral nephrectomy and adenine gavage, and animals were randomized into sham, model, and roxadustat (50 or 100 mg/kg, three times weekly) groups for 8 weeks. Renal function, hematological indices, calcium-phosphate parame-ters, and femoral microarchitecture were evaluated, and target protein levels (FGF23, FGFR1, DKK1, β-catenin) were assessed by Western blotting and immunohistochemistry. Roxadustat improved renal function, ameliorated the reduction in erythroid parameters, and restored calcium-phosphate homeostasis. Systemically, it mitigated micro-inflammation by reducing serum CRP and hepcidin, and downregulated serum FGF23 levels as well as tissue FGF23 expression in kidney and bone. In conclusion, the bone-protective effect of roxadustat occurs synchronously with systemic micro-inflammation mitigation, FGF23 downregulation, and Wnt/β-catenin signaling restoration. These findings highlight its pleiotropic therapeutic potential in CKD-MBD management, suggesting a synergistic benefit associated with both systemic metabolic recovery and local skeletal regulation.
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BibTeX
@article{shan2026roxadustat,
title = {{Roxadustat ameliorates bone microarchitectural deterioration in CKD-MBD rats in association with mitigated systemic micro-inflammation and restored FGF23–Wnt/β-catenin signaling}},
author = {Zhenzhen Shan and Yan Liu and Xue Sun and Zhan Li and Jinlan Ma and Yanjun Wang and Shaozheng Ai and Yanyan Yang and Pengli Luo},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1957451},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1957451/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Roxadustat ameliorates bone microarchitectural deterioration in CKD-MBD rats in association with mitigated systemic micro-inflammation and restored FGF23–Wnt/β-catenin signaling
AU - Zhenzhen Shan
AU - Yan Liu
AU - Xue Sun
AU - Zhan Li
AU - Jinlan Ma
AU - Yanjun Wang
AU - Shaozheng Ai
AU - Yanyan Yang
AU - Pengli Luo
PY - 2026
DA - 2026/11/03
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1957451
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1957451/full
AB - Elevated FGF23 is associated with bone microarchitectural deterioration in chronic kidney dis-ease-mineral and bone disorder (CKD-MBD). While roxadustat (a HIF-PHI) is established for the treatment of renal anemia, its potential bone-protective effects in CKD-MBD remain unclear. We investigated whether roxadustat ameliorates femoral microarchitectural deterioration in CKD-MBD rats in association with FGF23 downregulation and restoration of Wnt/β-catenin signaling. A CKD-MBD rat model was established by unilateral nephrectomy and adenine gavage, and animals were randomized into sham, model, and roxadustat (50 or 100 mg/kg, three times weekly) groups for 8 weeks. Renal function, hematological indices, calcium-phosphate parame-ters, and femoral microarchitecture were evaluated, and target protein levels (FGF23, FGFR1, DKK1, β-catenin) were assessed by Western blotting and immunohistochemistry. Roxadustat improved renal function, ameliorated the reduction in erythroid parameters, and restored calcium-phosphate homeostasis. Systemically, it mitigated micro-inflammation by reducing serum CRP and hepcidin, and downregulated serum FGF23 levels as well as tissue FGF23 expression in kidney and bone. In conclusion, the bone-protective effect of roxadustat occurs synchronously with systemic micro-inflammation mitigation, FGF23 downregulation, and Wnt/β-catenin signaling restoration. These findings highlight its pleiotropic therapeutic potential in CKD-MBD management, suggesting a synergistic benefit associated with both systemic metabolic recovery and local skeletal regulation.
SN - 1663-9812
ER -