Effect of Human Wnt10b Transgene Overexpression on Peri-Implant Osteogenesis in Ovariectomized Rats

This study aimed to investigate the efficacy of human Wnt10b (hWnt10b) transgene expression in ovariectomized (OVX) rats to accelerate osseointegration around titanium implants, and to provide a new strategy for treating osteoporosis with implants. An in vivo osteoporosis model was generated via bilateral ovariectomy in rats, and changes in expression of Wnt pathway-related genes were investigated. In OVX rats with a femur defect, hWnt10b expressed from an adenovirus vector was locally delivered to the defect site prior to implant placement. Surrounding femur tissues were collected 1 and 3 weeks after implantation for imaging, biomechanical testing, and molecular and histological analyses. In an in vitro model, bone-marrow stromal cells (BMSCs) transfected with adenovirus containing hWnt10b (Ad-hWnt10b) were cultured for 2 weeks in adipogenic medium followed by 2 weeks in osteogenic induction medium. Alizarin Red staining and Oil Red O staining, as well as reverse transcription polymerase chain reaction and Western blot analyses, were performed to assess the effect of hWnt10b expression on BMSC differentiation. Expression of Wnt pathway genes was significantly downregulated in OVX rats. OVX rats treated with Ad-hWnt10b prior to induction of a femur defect showed markedly increased ALP, Runx-2, and osteocalcin expression and decreased cathepsin K expression. Histological and imaging analysis showed increases in the number of osteocalcin-positive cells and the density of newly formed bone surrounding the implant in the Ad-hWnt10b group relative to the untreated control. Meanwhile, Ad-hWnt10b-BMSCs showed significantly increased osteogenesis and decreased adipogenesis. hWnt10b may accelerate osseointegration around implants and subsequently enhance bone regeneration and implant stabilization under OVX conditions.