2. Academic Validation
  3. LncRNA NR_045147 modulates osteogenic differentiation and migration in PDLSCs via ITGB3BP degradation and mitochondrial dysfunction

LncRNA NR_045147 modulates osteogenic differentiation and migration in PDLSCs via ITGB3BP degradation and mitochondrial dysfunction

  • Stem Cells Transl Med. 2024 Dec 14:szae088. doi: 10.1093/stcltm/szae088.
Lujue Long 1,  Chen Zhang 1,  Zhengquan He 2,  Ousheng Liu 3,  Haoqing Yang 1,  Zhipeng Fan 1 4 5
Affiliations

Affiliations

  • 1 Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China.
  • 2 Department of Orthodontics, Changsha Stomatology Hospital, Changsha, Hunan, People's Republic of China.
  • 3 Hunan Key Laboratory of Oral Health Research, Hunan 3D Printing Engineering Research Center of Oral Care, Academician Workstation for Oral-Maxilofacial and Regenerative Medicine, Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Xiangya Stomatological Hospital, Xiangya School of Stomatology, Central South University, Changsha, Hunan, People's Republic of China.
  • 4 Beijing Laboratory of Oral Health, Capital Medical University, Beijing, People's Republic of China.
  • 5 Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
PMID: 39674578 DOI: 10.1093/stcltm/szae088
Abstract

Periodontitis is an inflammation of the alveolar bone and soft tissue surrounding the teeth. Although mesenchymal stem cells (MSCs) have been implicated in periodontal regeneration, the mechanisms by which they promote osteogenesis remain unclear. We examined whether epigenetic modifications mediated by the long-noncoding RNA (lncRNA) NR_045147, which plays a crucial role in Cancer, influence the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Alkaline Phosphatase staining, alizarin red staining, and western blotting were used to detect the effects of NR_045147 on PDLSC osteogenic differentiation. Scratch migration and transwell chemotaxis assays were used to evaluate the effects of NR_045147 on PDLSC migration. Mitochondrial function was evaluated via Seahorse XF analysis to measure changes in cellular respiration upon manipulation of NR_045147 expression. Ubiquitination assays were performed to examine the protein stability and degradation pathways affected by the NR_045147-MDM2 interaction. An in vivo nude rat calvarial defect model was established and gene-edited PDLSCs were re-implanted to examine the osteogenic effects of NR_045147. NR_045147 significantly reduced PDLSC osteogenic differentiation and migration ability both in vitro and in vivo. Under inflammatory conditions, the loss of NR_045147 rescued osteogenesis. NR_045147 significantly blocked the expression of Integrin beta3-binding protein (ITGB3BP). Mechanistically, NR_045147 promoted the ITGB3BP-MDM2 interaction, thus increasing ITGB3BP ubiquitination and degradation. NR_045147 regulated PDLSC mitochondrial respiration and ITGB3BP upregulation efficiently promoted their osteogenic differentiation and migration ability. Concluding, NR_045147 downregulation enhances PDLSC osteogenic differentiation and migration, connects changes in cellular metabolism to functional outcomes via mitochondrial respiration, and promotes ITGB3BP degradation by mediating its interaction with MDM2.

Keywords

animal models; cell migration; differentiation; gene therapy; tissue regeneration.

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