Growth differentiation factor 11 impairs titanium implant healing in the femur and leads to mandibular bone loss.

BACKGROUND

Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor-β superfamily, has recently been suggested as an anti-aging factor that declines with age in the bloodstream, and restoration of the youthful level by administration of its recombinant protein could reverse age-related dysfunctions. However, its effects on titanium implant osseointegration and mandibular bone during aging remain unknown.

METHODS

Two-month-old and 18-month-old C57BL male mice were given daily intraperitoneal injections of recombinant GDF11 (rGDF11) or vehicle for 6 weeks. Experimental titanium implants were inserted into femurs on the fourth week. Inhibition of GDF11 function was achieved by GDF11 antibody. Implant-bearing femurs were subjected to histomorphometric analysis and biomechanical evaluation. Mandibles were scanned with micro-CT and decalcified for histological measurements.

RESULTS

In both young adult and aged mice, supraphysiologic GDF11 leads to a significantly decreased bone-to-implant contact ratio (BIC) and peri-implant bone volume/total volume (BV/TV) at the histologic level and reduced resistance at the biomechanical level, indicating weakened implant fixation. Moreover, rGDF11 administration resulted in less trabecular bone volume and thinner cortical thickness in the mandible, which was further compromised in the old animals. In contrast, inhibition of GDF11 improved peri-implant bone healing in old mice.

CONCLUSIONS

Rather than functioning as a rejuvenating factor, exogenous GDF11 negatively affects not only titanium implant healing but also mandibular bone in both young and old mice. In contrast, neutralization of endogenous GDF11 has positive effects on implant fixation in aged mice.