Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression. / Bogdanova, Evdokia; Sadykov, Airat; Ivanova, Galina; Zubina, Irina; Beresneva, Olga; Semenova, Natalia; Galkina, Olga; Parastaeva, Marina; Sharoyko, Vladimir; Dobronravov, Vladimir.
In: International Journal of Molecular Sciences, Vol. 24, No. 8, 7270, 14.04.2023.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression
AU - Bogdanova, Evdokia
AU - Sadykov, Airat
AU - Ivanova, Galina
AU - Zubina, Irina
AU - Beresneva, Olga
AU - Semenova, Natalia
AU - Galkina, Olga
AU - Parastaeva, Marina
AU - Sharoyko, Vladimir
AU - Dobronravov, Vladimir
PY - 2023/4/14
Y1 - 2023/4/14
N2 - The initial phases of molecular and cellular maladaptive bone responses in early chronic kidney disease (CKD) remain mostly unknown. We induced mild CKD in spontaneously hypertensive rats (SHR) by either causing 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, respectively). Sham-operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with a two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. Upon follow-up completion in each animal, we measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, Dickkopf-1, sclerostin, and assessed bone response by static histomorphometry and gene expression profiles. The mild CKD groups had no increase in renal Pi excretion, FGF23, or PTH levels. Serum Pi, Dickkopf-1, and sclerostin were higher in Nx6. A decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast numbers. The decline in eroded perimeter, a resorption index, 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. We found an association between mild CKD and histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.
AB - The initial phases of molecular and cellular maladaptive bone responses in early chronic kidney disease (CKD) remain mostly unknown. We induced mild CKD in spontaneously hypertensive rats (SHR) by either causing 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, respectively). Sham-operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with a two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. Upon follow-up completion in each animal, we measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, Dickkopf-1, sclerostin, and assessed bone response by static histomorphometry and gene expression profiles. The mild CKD groups had no increase in renal Pi excretion, FGF23, or PTH levels. Serum Pi, Dickkopf-1, and sclerostin were higher in Nx6. A decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast numbers. The decline in eroded perimeter, a resorption index, 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. We found an association between mild CKD and histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.
KW - Animals
KW - Creatinine/metabolism
KW - Fibroblast Growth Factors/metabolism
KW - Gene Expression
KW - Kidney/metabolism
KW - Osteogenesis
KW - Parathyroid Hormone/metabolism
KW - Phosphate Transport Proteins/metabolism
KW - Phosphates/metabolism
KW - Rats
KW - Renal Insufficiency, Chronic/complications
KW - Signal Transduction
KW - chronic kidney disease
KW - static bone histomorphometry
KW - inorganic phosphate transporters
KW - intracellular signaling
KW - bone remodeling
UR - https://www.mendeley.com/catalogue/4708c3df-7647-364b-9fb1-d0fe50aa02bd/
U2 - 10.3390/ijms24087270
DO - 10.3390/ijms24087270
M3 - Article
C2 - 37108433
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 8
M1 - 7270
ER -
ID: 114435848