Long Non-coding RNA TLX1NB Regulates Inflammatory Response in Periodontitis by Interacting With Matrix Metalloproteinase 8.

Long non-coding RNAs (lncRNAs) play critical roles in regulating inflammatory responses in periodontitis. This investigation focused on the involvement of the lncRNA T cell leukemia homeobox 1 neighbor (TLX1NB) in periodontitis and its regulatory role in modulating matrix metalloproteinase 8 (MMP8). Transcriptome sequencing and RT-qPCR validation revealed a significant upregulation of TLX1NB in gingival tissues from patients with periodontitis. This upregulation was recapitulated in an in vitro inflammatory model using TNF-α-stimulated human gingival fibroblasts (HGFs). Both FISH and cellular fractionation assays demonstrated that TLX1NB is predominantly enriched in the nucleus of HGFs. Functionally, TLX1NB knockdown attenuated the production of key pro-inflammatory cytokines, including IL-1β, IL-6, and IL-8, in TNF-α-stimulated HGFs, while concurrently enhancing cell proliferation. Mechanistically, RNA pull‑down and RIP assays confirmed a direct molecular interaction between TLX1NB and MMP8, suggesting that TLX1NB may regulate MMP8 function through direct binding. Functional analysis further demonstrated that TLX1NB and MMP8 act cooperatively to regulate inflammatory responses and apoptosis in HGFs. Ultimately, our results show that reducing TLX1NB expression alleviates periodontitis-associated inflammation and cellular dysfunction. This effect is associated with MMP8 and correlates with decreased NF-κB signaling. Collectively, these findings highlight TLX1NB as a promising therapeutic target for the treatment of periodontal disease.