Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The effect of nitrogen containing bisphosphonates, zoledronate and alendronate, on the production of pro-angiogenic factors by osteoblastic cells

Ishtiaq, S., Edwards, S., Sankaralingam, A., Evans, Bronwen Alice James, Elford, Carole, Frost, M.L., Fogelman, I. and Hampson, G. 2015. The effect of nitrogen containing bisphosphonates, zoledronate and alendronate, on the production of pro-angiogenic factors by osteoblastic cells. Cytokine 71 (2) , pp. 154-160. 10.1016/j.cyto.2014.10.025

Full text not available from this repository.

Abstract

Bisphosphonates (BPs) have been shown to influence angiogenesis. This may contribute to BP-associated side-effects such as osteonecrosis of the jaw (ONJ) or atypical femoral fractures (AFF). The effect of BPs on the production of angiogenic factors by osteoblasts is unclear. The aims were to investigate the effect of (1) alendronate on circulating angiogenic factors; vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG-1) in vivo and (2) zoledronate and alendronate on the production of VEGF and ANG-1 by osteoblasts in vitro. We studied 18 post-menopausal women with T score ⩽ −2 randomized to calcium/vitamin D only (control arm, n = 8) or calcium/vitamin D and alendronate 70 mg weekly (treatment arm, n = 10). Circulating concentrations of VEGF and ANG-1 were measured at baseline, 3, 6 and 12 months. Two human osteoblastic cell lines (MG-63 and HCC1) and a murine osteocytic cell line (MLO-Y4) were treated with zoledronate or alendronate at concentrations of 10−12–10−6 M. VEGF and ANG-1 were measured in the cell culture supernatant. We observed a trend towards a decline in VEGF and ANG-1 at 6 and 12 months following treatment with alendronate (p = 0.08). Production of VEGF and ANG-1 by the MG-63 and HCC1 cells decreased significantly by 34–39% (p < 0.01) following treatment with zoledronate (10−9–10−6 M). Treatment of the MG-63 cells with alendronate (10−7 and 10−6) led to a smaller decrease (25–28%) in VEGF (p < 0.05). Zoledronate (10−10–10−6 M) suppressed the production of ANG-1 by MG-63 cells with a decrease of 43–49% (p < 0.01). Co-treatment with calcitriol (10−8 M) partially reversed this zoledronate-induced inhibition. BPs suppress osteoblastic production of angiogenic factors. This may explain, in part, the pathogenesis of the BP-associated side-effects.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Osteoblasts; Bisphosphonates; Angiogenesis; VEGF; Angiopoietin-1
Publisher: Elsevier
ISSN: 1043-4666
Date of Acceptance: 28 October 2014
Last Modified: 12 Jun 2019 09:16
URI: http://orca-mwe.cf.ac.uk/id/eprint/85360

Citation Data

Cited 15 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item