Bogdanova, E.; Sadykov, A.; Ivanova, G.; Zubina, I.; Beresneva, O.; Semenova, N.; Galkina, O.; Parastaeva, M.; Sharoyko, V.; Dobronravov, V. Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression. Int. J. Mol. Sci.2023, 24, 7270.
Bogdanova, E.; Sadykov, A.; Ivanova, G.; Zubina, I.; Beresneva, O.; Semenova, N.; Galkina, O.; Parastaeva, M.; Sharoyko, V.; Dobronravov, V. Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression. Int. J. Mol. Sci. 2023, 24, 7270.
Bogdanova, E.; Sadykov, A.; Ivanova, G.; Zubina, I.; Beresneva, O.; Semenova, N.; Galkina, O.; Parastaeva, M.; Sharoyko, V.; Dobronravov, V. Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression. Int. J. Mol. Sci.2023, 24, 7270.
Bogdanova, E.; Sadykov, A.; Ivanova, G.; Zubina, I.; Beresneva, O.; Semenova, N.; Galkina, O.; Parastaeva, M.; Sharoyko, V.; Dobronravov, V. Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression. Int. J. Mol. Sci. 2023, 24, 7270.
Abstract
Background: Initial phases of molecular and cellular maladaptive bone response at early CKD remain mostly unknown. Methods: We induced mild CKD in SHRs by either arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, correspondently). Sham operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. We measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact PTH and FGF23, Klotho, dickkopf-1, sclerostin. And assessed bone response by static histomorphometric indices and gene expression profiles. Results: Mild CKD groups had no increase in renal Pi excretion, FGF23 and PTH levels. Serum Pi, dickkopf-1, and sclerostin were higher in Nx6. Decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast number. The decline in eroded perimeter was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. Conclusions: We found an association of mild CKD with histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.
Keywords
Chronic kidney disease; bone remodeling; static bone histomorphometry; inorganic phosphate transporters; intracellular signaling
Subject
Medicine and Pharmacology, Pathology and Pathobiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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