Low bone turnover in chronic kidney disease is associated with decreased VEGF-A expression and osteoblast differentiation

Neal X. Chen, Kalisha D. O'Neill, Matthew R. Allen, Christopher L. Newman, Sharon M. Moe

Research output: Contribution to journalArticle

9 Scopus citations

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 (US)
Pages (from-to)464-473
Number of pages10
JournalAmerican journal of nephrology
Volume41
Issue number6
DOIs
StatePublished - Aug 25 2015

Keywords

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

ASJC Scopus subject areas

  • Nephrology

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