Hydroxyapatite with High Carbonate Substitutions Promotes Osteoclast Resorption through Osteocyte-like Cells

The role of ceramic biomaterials in the repair of bone defects varies from materials that purely fill the physical defects of the injured bone to scaffolds that control cellular behaviors. In this study, we investigated the osteoclast formation related to the osteoconductivity of ceramic biomaterials. We performed in vitro cocultures using osteocyte-like cells and bone marrow cells and in vivo implantations of hydroxyapatite with different amounts of carbonate substitutions into rat femurs. The analyses of the cocultures revealed that bone marrow cells differentiated into osteoclasts and were activated to resorb the substratum when grown on hydroxyapatite with higher numbers of carbonate substitutions. This was indicated by the expression of macrophage colony-stimulating factor and receptor activator of the nuclear factor-kappa B ligand that induce osteoclast differentiation by osteocyte-like cells and characteristic resorption pits. The increased osteoclastogenesis in vivo was observed near the hydroxyapatite with more carbonate substitutions after implantation into the rat femurs. These results suggest that the content of carbonate ions in an apatite crystal lattice has an inductive effect on osteoclastogenesis in the vicinity of the implanted ceramic biomaterial. The results contribute to the design of biomaterials that would be resorbed by osteoclasts after fulfilling their primary function as scaffolds for cell growth and eventually bone regeneration.