Synergistic effects of lipopolysaccharide and titanium ions on monocytic myeloid-derived suppressor cell expansion in gingival tissue: implications for peri-implant bone health

Purpose: Titanium particles and ions detected in peri-implant tissues have been implicated in crestal bone loss around dental implants. However, their precise effects on adjacent peri-implant structures remain insufficiently understood. This study investigates the impact of foreign body reactions induced by titanium ions on peri-implant bone levels, with a specific focus on monocytic myeloid-derived suppressor cells (M-MDSCs), which have been reported to possess osteoclast precursor potential. Methods: Bone marrow, spleen, and gingival cells were exposed to titanium ions and lipopolysaccharide (LPS) to evaluate M-MDSC differentiation using flow cytometry. In addition, an in vivo mouse model with titanium implants was employed to assess M-MDSC proliferation, phenotypic characteristics, and associated peri-implant bone changes. Results: Titanium ions enhanced the differentiation of M-MDSCs and macrophages from bone marrow-derived precursors. In vitro experiments demonstrated that titanium ions and LPS synergistically increased M-MDSC populations. In vivo, mice with ligature-induced peri-implantitis surrounding titanium implants exhibited a significant increase in M-MDSCs within peri-implant tissues. Notably, these M-MDSCs showed upregulated expression of the osteoclastogenic receptor c-Fms (CD115), indicating a primed state for osteoclast differentiation. This cellular shift was accompanied by a corresponding reduction in peri-implant bone mineral density and bone volume when compared with mice bearing implants alone. Conclusions: Titanium ions and inflammatory stimuli synergistically promote not only the expansion of M-MDSCs but also their osteoclastogenic priming. These findings suggest that primed M-MDSCs may function as key cellular mediators in the pathogenesis of peri-implantitis. Furthermore, they highlight M-MDSCs as a potential therapeutic target for improving implant longevity and underscore the importance of controlling peri-implant inflammation.