In Vivo Evaluation of the Adenovirus-Mediated Sox9 and BMP2 Double Gene Transduction on Treatment of Intervertebral Disc Degeneration in Rabbit Annular Puncture Model

摘要

Objective: To investigate the biological effects of the SRY-box 9 (Sox9) and bone morphogenetic protein-2 (BMP2) mediated by adenovirus on the disc degeneration in vivo. Methods: The acquired BMSCs were transduced with adenovirus (AdV)-mediated Sox9 and BMP2, respectively. Then, the gene-modified BMSCs were combined with platelet-rich plasma (PRP), and transplanted into the rabbit disc degeneration model. After disc degeneration induction, fifty New Zealand white rabbits were randomly divided into five groups: Double gene; Sox9, BMP2; BMSCs and disc degeneration groups. Imaging evaluation, histological staining, reverse transcription PCR (RT-PCR), immune-histochemical analysis, and western blotting were performed on 6th and 12th week after transplantation. Results X-ray and MRI showed that the disc height and T2-weighted signal intensity were significantly restored in double and single gene groups (P 0.05), with significantly difference between the double and single gene group at each testing point (P 0.05). RT-PCR, immune-histochemical analysis, and western blotting showed that expressions of collagen II and aggrecan in the double gene group were significantly higher than the single gene groups (P 0.05). Conclusions: The AdV-mediated SOX9 and BMP2 can effectively repair the histological structures and promote the extracellular matrix synthesis of degenerative IVDs. The synergistic therapeutic effects of the double gene therapy on disc degeneration in vivo is superior to those of the single gene therapy.