Systemic administration of cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4)‐Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation

Background/objectives Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule expressed on cells. CTLA-4 also binds to the surfaces of monocytes and macrophages, precursors osteoclasts. Research rheumatoid arthritis demonstrated that suppresses inflammation bone resorption. However, its effects alveolar have yet be understood. The purpose this study was investigate role potential mechanism in resorption periodontitis. Materials methods In vivo, systemic administration immunoglobulin fusion protein (CTLA-4-Ig) were investigated using periodontitis mouse model. A total 20 C57BL/6J mice randomly assigned two groups according modes. Periodontitis induced by placing ligature around left maxillary second molar. contralateral tooth un-ligated. CTLA-4-Ig (+) group, administered intraperitoneal injection at 1 3 days after placement. Animals (−) group given only phosphate-buffered saline each time. At 5 placement, assessed micro-computed tomography histological examination, prevalence osteoclast-like cells tartrate-resistant acid phosphatase (TRAP) staining. vitro, osteoclasts evaluated. Viability RAW 264.7 treated with receptor activator nuclear factor-κB ligand (RANKL) tested WST-1 assay. Osteoclast-like enumerated TRAP staining, osteoclast activity evaluated pit Gene expression levels differentiation markers (macrophage-colony stimulating factor receptor, carbonic anhydrase II, cathepsin K, Trap) 2A (PP2A), major serine-threonine phosphatase, quantitative real-time polymerase chain reaction. effect (NF-κB) activation enzyme-linked immunosorbent Results ligature-induced numbers significantly decreased CTLA-4-Ig. treatment RANKL had no significant cell viability. reduced expressions markers, compared RANKL-treated control. suppressed RANKL-induced phosphorylation NF-κB p65 but increased PP2A expression. Conclusion These results suggest abrogates periodontitis, possibly via inhibition activation. regulation pathway may one which behavior.