Effect of lentiviral vector overexpression α-calcitonin gene-related peptide on titanium implant osseointegration in α-CGRP-deficient mice.

Abstract

α-Calcitonin gene-related peptide (α-CGRP) plays a significant pathophysiological role in bone development, metabolism and remodeling around dental implants. However, the half-life of α-CGRP in plasma is only 10min, which affects its long-time application and an alternative approach should be developed to deliver α-CGRP over long periods of time. The aim of this study is to investigate whether a lentiviral α-CGRP overexpression vector system can express this target-gene longer at peri-implant sites, thus enhancing osseointegration. Animals were divided to the following groups: α-CGRP^-/-, α-CGRP^-/- with lentivirus transfection and α-CGRP^+/+ mice. IVIS Spectrum imaging observations identified the successful transfection of α-CGRP around experimental implants inserted in the femurs at 5days after injection. Histomorphometrical analysis indicated an increase of bone-implant contact (BIC) at 1-month healing in the transfection group. Moreover, real-time RT-PCR and western blot results of bone-related markers Runx2, Osterix, and BSP levels elevated in lentivirus-transfected mice at 21days, compared to the untreated α-CGRP^-/- mice. There was no significant difference between the transfection group and α-CGRP^+/+ group. Further α-CGRP protein detection confirmed the persistent expression of this transgene at 21days post-operatively. These results suggest that this lentiviral vector system expresses α-CGRP in an effective, appropriate and sustained manner, which might have a potential application in enhancing titanium implant osseointegration.