Low Bone Turnover in Chronic Kidney Disease Is Associated with Decreased VEGF-A Expression and Osteoblast Differentiation
Low Bone Turnover in Chronic Kidney Disease Is Associated with Decreased VEGF-A Expression and Osteoblast Differentiation
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DOI：
10.1159/000438461
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发表时间：
2015-01-01
影响因子：
4.2
通讯作者：
Moe, Sharon M.
中科院分区：
文献类型：
--
作者：
Chen, Neal X.;O'Neill, Kalisha D.;Moe, Sharon M.
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-1 alpha 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. (C) 2015 S. Karger AG, Basel
