Dectin-2 depletion alleviates osteoclast-induced bone loss in periodontitis via Syk/NOX2/ROS signaling.

Abstract

Periodontitis is the sixth most common disease worldwide and is closely associated with various systemic diseases, impacting overall health. It is characterized by the over-differentiation and activity of osteoclasts, leading to increased bone resorption and subsequent bone loss. Current treatments for bone loss are not ideal, highlighting the need for new targeted therapeutic strategies. Dectin-2, a member of the C-type lectin receptor (CLR) family, has recently been reported to play an important role in immune regulation, but its role in osteoclastogenesis has not been documented. This study identified a significant upregulation of Dectin-2 expression during osteoclast differentiation through single-cell sequencing and transcriptomic analysis. Knocking down Dectin-2 significantly inhibits the differentiation of RAW264.7 cells and bone marrow-derived macrophages (BMDMs) into osteoclasts, while overexpressing Dectin-2 enhances osteoclast differentiation and function. Mechanistically, transcriptomic analysis indicates that Dectin-2 deficiency disrupts redox homeostasis and affects the MAPK signaling pathway. Furthermore, the study demonstrates that Dectin-2 promotes osteoclastogenesis via the Syk/NOX2/ROS/MAPK signaling axis. In vivo, Dectin-2 knockout mice show reduced osteoclast numbers and decreased alveolar bone resorption in a periodontitis model. In conclusion, these findings suggest that Dectin-2 is a key regulatory factor in osteoclast-mediated bone resorption and may serve as a promising therapeutic target for bone diseases characterized by osteoclast overactivity, such as periodontitis.