Endolysin XZ.700 preserves the functional activity of osteoclasts and foreign body giant cells on a bone substratum

Periprosthetic bacterial infection is a major challenge in orthopedics and dentistry. The novel bacteriophage-derived endolysin XZ.700 has been developed to treat implant-associated bacterial infections. It exhibits low osteoblast-toxicity, and reduces osteoclast and foreign body giant cell formation on plastic substratum, suggesting short-term administration as a safe strategy. However, whether endolysin XZ.700 affects osteoclast and foreign body giant cell function in a bone microenvironment remains unknown. Therefore, this study aimed to investigate whether endolysin XZ.700 affects osteoclast and foreign body giant cell function in an in vitro model with a bone substratum. Differentiation of monocytes into multinucleated osteoclasts and foreign body giant cells from CD14⁺ monocytes cultured on bone substratum with/without endolysin XZ-700 (75 μg/ml) was determined, as well as their function up to 21 days. Endolysin XZ.700 did not affect bone resorption, extracellular secreted tartrate-resistant acid phosphatase, matrix metalloproteinase-2 and 9 activity, and inflammatory and differentiation-related gene expression by osteoclasts and foreign body giant cells. However, endolysin XZ.700 downregulated expression of function-related gene CTSK (336.1-fold, p < 0.05, day 21) in osteoclasts, but upregulated CTSK (4.0-fold, p < 0.05, day 14) and multinucleation-related gene DC-STAMP (2.3-fold, p < 0.05, day 7) expression in foreign body giant cells. In conclusion, endolysin XZ.700 did not affect differentiation of osteoclasts and foreign body giant cells from monocytes and their function in an in vitro model with a bone substratum mimicking the natural bone microenvironment, indicating that it might be promising to treat implant-associated bacterial infections.