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

Oral Dis. 2022 Oct;28(7):1958-1967. doi: 10.1111/odi.13888. Epub 2021 May 10.

Abstract

Background: 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.

Methods: 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.

Results: 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.

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

Keywords: TRIM14; inflammatory responses; noncanonical NF-κB signaling; osteoclastogenesis.

MeSH terms

  • Animals
  • Chronic Periodontitis* / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • NF-kappa B / metabolism
  • NF-kappa B p52 Subunit / metabolism*
  • Osteoclasts
  • Osteogenesis
  • RANK Ligand / metabolism
  • Signal Transduction
  • Tripartite Motif Proteins / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Nfkb2 protein, mouse
  • RANK Ligand
  • Trim14 protein, mouse
  • Tripartite Motif Proteins