Effects of erythromycin on osteoclasts and bone resorption via del‐1 induction in mice

Abstract

Macrolides are used to treat various infectious diseases, including periodontitis. Further-more, macrolides are known to have immunomodulatory effects; however, the underlying mechanism of their action remains unclear. DEL‐1 has emerged as an important factor in homeostatic immunity and osteoclastogenesis. Specifically, DEL‐1 is downregulated in periodontitis tissues. There-fore, in the present study, we investigated whether the osteoclastogenesis inhibitory effects of eryth-romycin (ERM) are mediated through upregulation of DEL‐1 expression. We used a ligature‐in-duced periodontitis model in C57BL/6Ncrl wild‐type or DEL‐1‐deficient mice and in vitro cell‐based mechanistic studies to investigate how ERM inhibits alveolar bone resorption. As a result of meas-uring alveolar bone resorption and gene expression in the tooth ligation model, ERM treatment reduced bone loss by increasing DEL‐1 expression and decreasing the expression of osteoclast‐re-lated factors in wild‐type mice. In DEL‐1‐deficient mice, ERM failed to suppress bone loss and gene expression of osteoclast‐related factors. In addition, ERM treatment downregulated osteoclast differentiation and calcium resorption in in vitro experiments with mouse bone marrow‐derived mac-rophages. In conclusion, ERM promotes the induction of DEL‐1 in periodontal tissue, which may regulate osteoclastogenesis and decrease inflammatory bone resorption. These findings suggest that ERM may exert immunomodulatory effects in a DEL‐1‐dependent manner.