Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo

Owing to its bio- and osteoconductivity, hydroxyapatite (HA) is a widely used implant material, but its osteogenic properties are only partly evaluated in vitro and in vivo. The present study focused on bone healing adjacent to HA-coated titanium (Ti) implants, with or without incorporated lithium ions (Li⁺). Special attention was given to the Wnt signaling pathway. The implants were inserted into rat tibia for 7 or 28 days and analyzed ex vivo, mainly by histomorphometry and quantitative real-time polymerase chain reaction (qPCR). HA-coated implants showed, irrespective of Li⁺ content, bone-implant contact (BIC) and removal torque values significantly higher than those of reference Ti. Further, the expression of OCN, CTSK, COL1A1, LRP5/6 and WISP1 was significantly higher in implant-adherent cells of HA-coated implants, with or without Li⁺. Significantly higher β-catenin expression and significantly lower COL2A1 expression were observed in peri-implant bone cells from HA with 14 ng cm^-2 released Li⁺. Interestingly, Ti implants showed a significantly larger bone area (BA) in the threads than HA with 39 ng cm^-2 released Li⁺, but had a lower BIC than any HA-coated implant. This study shows that HA, with or without Li⁺, is a strong activator of the Wnt signaling pathway, and may to some degree explain its high bone induction capacity.