Sidt2 Knockdown Aggravates Apical Periodontitis Via Autocrine Tumour Necrosis Factor-Alpha

Area of Science:

• Biomedical Science
• Immunology
• Oral Biology

Background:

• Apical periodontitis (AP) involves inflammation and bone loss, with high tumour necrosis factor-alpha (TNF-α) expression.
• SID1 transmembrane family member 2 (Sidt2), a lysosomal protein, is implicated in inflammation, but its role in AP is unknown.

Purpose of the Study:

• To investigate the effect of Sidt2 on apical periodontitis (AP) and its underlying mechanisms.
• To explore Sidt2's role in inflammation and osteoclast differentiation in AP.

Main Methods:

• An AP mouse model was created, with Sidt2 expression inhibited using adenovirus-associated virus.
• Micro-computed tomography, histological staining, and molecular analyses (qPCR, Western blot, ELISA, RNA sequencing) were performed.
• Osteoclast differentiation and TNF-α signaling were assessed in vivo and in vitro (RAW 264.7 cells).

Main Results:

• Sidt2 expression was suppressed, while TNF-α increased in AP models.
• Sidt2 inhibition exacerbated inflammation and bone loss in AP, upregulating osteoclast differentiation.
• Sidt2 knockdown enhanced TNF-α production; neutralizing TNF-α partially reversed Sidt2 inhibition-induced osteoclast differentiation.

Conclusions:

• Sidt2 negatively regulates autocrine TNF-α signaling, impacting osteoclast differentiation in AP.
• Sidt2 represents a potential therapeutic target for managing bone resorption in AP.