Trim14 promotes osteoclastogenesis and noncanonical NF-κB activation by targeting p100/p52 in chronic periodontitis

Periodontitis disease infection initiates host immune response, and alveolar bone damage is a hallmark of periodontitis. Bone damage occurs due to changes in osteoclast activity in response to local inflammation. Nuclear factor κB (NF-κB) signaling is essential for inflammatory responses and plays a pivotal role in osteoclast formation and activation. Tripartite motif 14 (Trim14) is a crucial regulator of the noncanonical NF-κB signaling. Here, we investigated the role of Trim14 in chronic periodontitis.

The development of immune cells and osteoclast formation was evaluated with flow cytometry, qRT-PCR, and histochemical staining. Proinflammatory cytokines were checked by ELISA and qRT-PCR. Protein expression was determined by immunoblotting. Also, the cemento-enamel junction-alveolar bone crest distance was evaluated in the mouse model.

Development of innate and adaptive cells was not impaired from the deletion of Trim14. However, the genetic loss of Trim14 remarkably suppressed RANKL-induced osteoclastogenesis, without affecting TLR-induced proinflammatory cytokines except for Il-23a expression. The Trim14 deletion also suppressed the activation of noncanonical NF-κB signaling by targeting p100/p52. Importantly, the deletion of NIK diminished the effects of Trim14 on the inflammatory responses in vivo on chronic periodontitis responses.

TRIM14 may be a positive regulator to promote osteoclastogenesis and proinflammatory cytokine secretion.