Low Bone Turnover in Chronic Kidney Disease Is Associated with Decreased VEGF-A Expression and Osteoblast Differentiation

Xuening (Neal) Chen, Kalisha D. O''Neill, Matthew Allen, Christopher L. Newman, Sharon Moe

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Low turnover bone (low bone formation rates (BFRs)) with decreased osteoblast number is common in patients with chronic kidney disease (CKD) and attributed to 'over-suppression' of the parathyroid hormone (PTH) despite supra-physiologic levels. An alternative hypothesis is abnormal osteoblast differentiation, resulting in low BFRs due to reduced VEGF-A. Methods: We analyzed the expression of VEGF-A and mesenchymal stem cell (MSC) differentiation factors in freshly isolated bone marrow (BM) cells, and in BM cell-derived MSC in rats with different levels of BFRs and PTH (modulated by calcium and zoledronic acid). The regulators of VEGF in MSC were also determined. Results: VEGF-A expression was reduced in the BM cells from CKD vs. normal animals (p < 0.02). In BM-derived MSC from CKD, there were decreased osteoblast transcription factors and mineralization. In CKD animals, the BM VEGF-A expression was positively correlated with BFR (r = 0.80, p < 0.001). Reducing BFRs in CKD animals led to reductions in VEGF-A expression and osteoblast transcription factors regardless of the PTH level. We therefore examined other regulators of VEGF-A and found decreased expression of hypoxia-inducible factor-1α and the master transcription factor of antioxidants nuclear factor (erythroid-derived 2)-like 2 in CKD animals with low PTH. Conclusion: Low BFRs in CKD are associated with a basal decrease in VEGF-A expression in BM that may be driven by altered hypoxia and oxidative stress.

Original languageEnglish
Pages (from-to)464-473
Number of pages10
JournalAmerican Journal of Nephrology
Volume41
DOIs
StatePublished - Aug 25 2015

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Bone Remodeling
Osteoblasts
Chronic Renal Insufficiency
Vascular Endothelial Growth Factor A
Osteogenesis
Parathyroid Hormone
Mesenchymal Stromal Cells
Bone Marrow Cells
Transcription Factors
zoledronic acid
Bone Marrow
Hypoxia-Inducible Factor 1
Stem Cell Factor
Cell Differentiation
Oxidative Stress
Antioxidants
Calcium
Bone and Bones

Keywords

  • Bone formation
  • Bone marrow cells
  • CKD
  • PTH
  • VEGF

ASJC Scopus subject areas

  • Nephrology

Cite this

Low Bone Turnover in Chronic Kidney Disease Is Associated with Decreased VEGF-A Expression and Osteoblast Differentiation. / Chen, Xuening (Neal); O''Neill, Kalisha D.; Allen, Matthew; Newman, Christopher L.; Moe, Sharon.

In: American Journal of Nephrology, Vol. 41, 25.08.2015, p. 464-473.

Research output: Contribution to journalArticle

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