Lrp5 A241T High-Bone-Mass Mutation Enhances Implant Osseointegration: An Experimental Murine Study

This study aimed to assess the effect of the low-density lipoprotein receptor-related protein 5 (Lrp5) A241T gain-of-function mutation, which induces a high-bone-mass phenotype, on implant osseointegration in a murine model.

Heterozygous Lrp5 A241T mutant (Lrp5^A/+) and wild-type (WT) littermate male mice on a C57BL/6J background were used. Micro-computed tomography (micro-CT) was performed to assess tibial trabecular bone architecture. Sandblasted and acid-etched (SLA) titanium implants were surgically inserted into the proximal tibiae, and samples were harvested after 4 weeks for micro-CT and histological analysis. Primary osteoblasts were seeded onto SLA titanium sheets and induced for osteogenesis for 7 days. Osteogenic marker expression was assessed by quantitative real-time polymerase chain reaction and western blotting.

The Lrp5^A/+ group exhibited significantly improved trabecular bone architecture compared to WT controls. At 4 weeks post-implantation, micro-CT revealed greater peri-implant bone formation in the Lrp5^A/+ group, while hard tissue sections showed increased bone area and bone-implant contact. HE and Masson staining further confirmed greater new bone formation. After 7 days of in vitro osteogenic induction, Lrp5, Runx2, and Sp7 were significantly upregulated in the Lrp5^A/+ group.

The Lrp5 A241T mutation significantly enhanced implant osseointegration in a transgenic murine model.