Bone-vascular axis: Regulation of vascularization by antiresorptive drugs

CUTINI P.; RAUSCHEMBERGER M.B.; MASSHEIMER V.

Ciudad Autónoma de Buenos Aires

Congreso; XXXI Reunión Anual de la AAOMM; 2014

Vascularization is essential in bone formation and remodeling as well as in fracture healing. Vascular endothelial growth factor (VEGF) is a key regulator in angiogenesis, a crucial process for new blood vessel formation from pre-existing vasculature. At bone level, VEGF promotes the canalicular flow and cartilage mineralization, and contributes to provide bone marrow progenitor cells. The aim of this study was to investigate the effects involved in neovascularization on molecular and cellular events (VEGF synthesis, nitric oxide (NO) production, ECs proliferation and migration) elicited by drugs used in bone pathologies. ECs primary cultures treated with the SERM raloxifene (Rx) or the bisphosphonate alendronate (ALN) were used. The effects of the drugs on VEGF production were studied using ELISA technique. Treatments for 24 h with 5 μM ALN or 10 nM Rx induced a marked stimulation of VEGF synthesis (21.03 ± 0.58; 33.26 ± 1.62; 27.32 ± 0.12 pg VEGF/mg protein, control; ALN; Rx, p b 0.05). Both drugs induced a significant stimulation on NO synthesis after 15 min of treatment (31.3± 2.9; 52.3± 4.6; 51.2 ±3.9 nmol NO/mg prot; control; 10 nM Rx; 5 μM ALN, pb 0.05). Using the MTT colorimetric assay, we showed that 24 h treatment with Rx significantly increased cell proliferation (75?94% over control; 1?10 nM Rx, p b 0.001). With respect to ECs migration, 72 h of treatment with Rx induced a significant stimulation of cellmobility (304 ± 29; 370 ± 25 cells/field, control; 10 nM Rx, p b 0.05). However, ALN treatment does not alter ECs proliferation and migration. These results suggest that ALNand Rx exhibit putative beneficial effects on new blood vessel formation. Rx modulates both cellular and molecular events, meanwhile the regulatory effect of ALN was elicited only at molecular level.