Adenovirus mediated gene delivery of α-calcitonin gene-related peptide facilitates osseointegration of implant in ovariectomized rat.

BACKGROUND

Osteoporosis, which adversely affected osseointegration of dental implants, became prevalent with the entry of ageing era. Recent studies indicated that α-calcitonin gene-related peptide (α-CGRP) played a role in modulating osteoporosis. However, due to the plasma half-life of α-CGRP being estimated at merely 7-10 min, it was difficult to utilize a conventional method that administered sufficient α-CGRP to the implant site. This present study aimed to investigate the efficacy of an α-CGRP transgene in promoting implant osseointegration in ovariectomized (OVX) rats.

METHOD: The osteoporosis rat model was established through bilateral ovariectomy, following which the subjects were categorized into three distinct groups: the α-CGRP transgene group, the empty virus vector group, and the blank control group. Ad-CGRP-EGFP was locally administered into the bone defect site prior to implant placement in the OVX rats. 7 and 28 days after implantation, the femurs were isolated for molecular and histological analyses, micro-CT analysis and biomechanical test.

RESULT: Bone marrow stromal cells (BMSCs) transduced with Ad-CGRP-EGFP could continuously express α-CGRP more than 28 days in vitro. Successful transgene expression was confirmed through cryosectioning and Western blot analysis 7 days after implantation in vivo. The results indicated a substantial decrease in the quantity of TRAP + cells in the α-CGRP transgene group. Additionally, quantitative real-time RT-PCR and Western blot analysis revealed a significant elevation in the expression levels of Runx2 and ALP, coupled with a notable reduction in the expression of cathepsin K and RANKL (P<0.05). Moreover, the α-CGRP transgene group exhibited a significant enhancement in osteointegration and restoration of implant stability in OVX rats (P<0.01) 28 days after implantation.

CONCLUSION

This study implied a great therapeutic potential of α-CGRP in osseointegration of titanium implants in OVX-relative osteoporosis rats, offering valuable insights for guiding bone regeneration strategies under osteoporotic conditions.