Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression.
Evdokia BogdanovaAirat SadykovGalina IvanovaIrina ZubinaOlga BeresnevaNatalia Yuryevna SemenovaOlga GalkinaMarina ParastaevaVladimir SharoykoVladimir DobronravovPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- chronic kidney disease
- bone mineral density
- end stage renal disease
- bone regeneration
- signaling pathway
- gene expression
- postmenopausal women
- soft tissue
- cell proliferation
- arterial hypertension
- dna methylation
- body composition
- stem cells
- uric acid
- genome wide
- oxidative stress
- robot assisted
- metabolic syndrome
- pi k akt
- drug induced
- mesenchymal stem cells
- epithelial mesenchymal transition
- single molecule
- transcription factor
- double blind
- liver fibrosis