Background: Adiponectin (APN) has been reported to promote bone formation. However, it is difficult to utilize a conventional method that administers sufficient APN to the implant site. The present study investigated the efficacy of an APN transgene to accelerate the implant osseointegration in ovariectomized (OVX) rats.
Methods: In vitro, bone marrow stromal cells were transduced with reconstructed adenovirus (Ad-APN-EGFP) and osteoclast precursor RAW264.7 cells were co-cultured with the conditioned medium secreted by transduced bone marrow stromal cells. Tartrate-resistant acid phosphatase staining and bone slice resorption assay were performed to evaluate the activity of osteoclastogenesis. In vivo, Ad-APN-EGFP was administered into the bone defect prior to implant placement in OVX rats. At 7 and 28 days post implantation, the femurs were harvested and prepared for a real-time reverse transcriptase-polymerase chain reaction, hemotoxylin and eosin staining, immunohistochemical staining, micro-computed tomography analysis and biomechanical testing.
Results: The results showed the formation and function of osteoclasts were significantly suppressed in vitro. Successful transgene expression was confirmed, and a significant increase of OCN, Runx2 and ALP expression was detected in the Ad-APN-EGFP group in vivo. Interestingly, we also found that the overexpression of APN decreased the expression level of potent adipogenic transcription factors such as PPARγ2 and C/EBP-α. At 28 days after implantation, the Ad-APN-EGFP group revealed a significantly increased osseointegration and implant stability in OVX rats compared to the control groups (Ad-EGFP and PBS groups).
Conclusions: APN via direct adenovirus-mediated gene transfer could ameliorate osseointegration surrounding titanium implants in OVX-related osteoporosis rats. Furthermore, it may be an effective strategy for promoting bone regeneration under osteoporotic conditions.
Keywords: adenovirus; adiponectin; differentiation; implant; osseointegration.
© 2019 John Wiley & Sons, Ltd.