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Biology of Pulpal and Periradicular Tissues

OR21 - Influence of Epigenetic and Extracellular Matrix Modulators on Dental Pulp Stem Cells

Wednesday, April 2, 2025
2:30 PM – 2:45 PM EST
Location: Hynes Convention Center, Floor 3, Room 309
Disclosure(s):
Xiaofei Zhu, DDS, CAGS: No financial relationships to disclose
Sami Chogle, D.M.D., B.D.S., M.S.D.: No financial relationships to disclose
Objective: Dental pulp stem cells (DPSCs) are multipotent mesenchymal stem cells, making them a valuable resource for regenerative applications. However, the effects of extracellular matrix (ECM) and epigenetic regulatory factors on DPSC maintenance and differentiation are poorly characterized. Previously, the epigenetic regulator Lysine Specific Demethylase 1(LSD1) and ECM-promoting protein Lysyl Oxidase Like 2 (LOXL2) have been studied in diverse stem cells. This research aims to elucidate the interplay between LSD1 and LOXL2 in DPSCs.

Methods: Human DPSCs, isolated from a patient under approved IRB, were treated in triplicate with an LSD1 inhibitor, LOXL2, and a combination of both. The outcomes were evaluated by RT-qPCR, confocal microscopy, proliferation, and apoptosis assays and analyzed using one-way ANOVA (p < 0.05).

Results: Reanalysis of single-cell RNA-seq (scRNA-seq) data showed that LSD1 and LOXL2 are expressed in human DPSCs. LSD1 inhibition by the small molecule inhibitor SP2509 resulted in reduced cell number and significant upregulation of ALP and BMP4 (p < 0.05), indicating a loss of stem cell characteristics and increased differentiation. SP2509 treatment also increased inflammatory factor NFkβ, and apoptosis marker Annexin V was evaluated by confocal imaging. LOXL2 treatment, in combination with SP2509, led to a partial reversal of these effects on DPSCs. Ongoing studies will characterize these in detail.

Conclusion: LSD1 inhibition enhances osteogenic and inflammatory signaling in human DPSCs, while LOXL2 co-treated with LSD1 inhibition counteracts these effects, highlighting a complex regulatory relationship. These insights could inform targeted strategies in pulp regeneration for clinical endodontic applications.