Other
15 Authors
- Jeong YN,
- Liu Y,
- Karimbux N,
- Chen JJ,
- Ma Q,
- Li RY,
- Zhu ZX,
- Van Dyke TE,
- Tai A,
- Wang J,
- Tu Q,
- Xie Y,
- Couldwell S,
- El-Araby RE,
- Melhem NA
| First Author | Zhu ZX | Year | 2023 |
| Journal | Int J Biol Sci | Volume | 19 |
| Issue | 16 | Pages | 5187-5203 |
| PubMed ID | 37928259 | Mgi Jnum | J:342363 |
| Mgi Id | MGI:7547783 | Doi | 10.7150/ijbs.87977 |
| Citation | Zhu ZX, et al. (2023) A novel lncRNA-mediated epigenetic regulatory mechanism in periodontitis. Int J Biol Sci 19(16):5187-5203 |
| abstractText | Periodontitis is a highly prevalent chronic inflammatory disease with an exaggerated host immune response, resulting in periodontal tissue destruction and potential tooth loss. The long non-coding RNA, LncR-ANRIL, located on human chromosome 9p21, is recognized as a genetic risk factor for various conditions, including atherosclerosis, periodontitis, diabetes, and cancer. LncR-APDC is an ortholog of ANRIL located on mouse genome chr4. This study aims to comprehend the regulatory role of lncR-APDC in periodontitis progression. Our experimental findings, obtained from lncR-APDC gene knockout (KO) mice with induced experimental periodontitis (EP), revealed exacerbated bone loss and disrupted pro-inflammatory cytokine regulation. Downregulation of osteogenic differentiation occurred in bone marrow stem cells harvested from lncR-APDC-KO mice. Furthermore, single-cell RNA sequencing of periodontitis gingival tissue revealed alterations in the proportion and function of immune cells, including T and B cells, macrophages, and neutrophils, due to lncR-APDC silencing. Our findings also unveiled a previously unidentified epithelial cell subset that is distinctively presenting in the lncR-APDC-KO group. This epithelial subset, characterized by the positive expression of Krt8 and Krt18, engages in interactions with immune cells through a variety of ligand-receptor pairs. The expression of Tff2, now recognized for its role in chronic inflammatory conditions, exhibited a notable increase across various tissue and cell types in lncR-APDC deficient mice. Additionally, our investigation revealed the potential for a direct binding interaction between lncR-APDC and Tff2. Intra-gingival administration of AAV9-lncR-APDC was shown to have therapeutic effects in the EP model. In conclusion, our results suggest that lncR-APDC plays a critical role in the progression of periodontal disease and holds therapeutic potential for periodontitis. Furthermore, the presence of the distinctive epithelial subpopulation and significantly elevated Tff2 levels in the lncR-APDC-silenced EP model offer new perspectives on the epigenetic regulation of periodontitis pathogenesis. |
