(PR157) Therapeutic Potential of Secreted Factors from Dental Pulp Stem Cells in Osteoarthritis

Objective: Dental Pulp Stem Cells (DPSCs) are a versatile population of mesenchymal stem cells derived from endodontic tissue with regenerative and anti-inflammatory properties. Osteoarthritis (OA), a chronic condition characterized by inflammation and cartilage degradation, leads to joint dysfunction and significant patient morbidity. Single-cell RNA sequencing (scRNA-seq) of DPSCs confirmed the expression of key regenerative and anti-inflammatory genes, including BDNF, MYC, RUNX2, BGLAP, BMP4, BMP1, NCAM1, NTF3, TGFB1, and LOXL2. This study hypothesizes that LOXL2-modulated DPSC secretome can mitigate inflammation, reduce apoptosis, and promote chondrocyte protection in OA.

Methods: Approximately 50,000 human DPSCs, obtained from a patient under IRB, were cultured and treated with control, IL-1β, IL-1β+Ad5-LOXL2, and Ad5-LOXL2. Conditioned media was collected and applied to normal chondrocytes, followed by RT-qPCR, apoptosis via FITC-Annexin V staining, and NFkB-p65 immunostaining, and analysis by one-way ANOVA.

Results: IL-1β significantly upregulated IFNβ levels by 10-fold (p < 0.05), NFkβ expression by 2-fold (p < 0.05), IL-1β levels by 2-fold (p < 0.05), and STAT3 expression by 2-fold (p < 0.05). Media from Ad5-LoxL2-treated DPSCs markedly downregulated these inflammatory markers, restoring them closer to baseline levels. Confocal microscopy confirmed reduced apoptosis and nuclear localization of activated NFkβ in chondrocytes treated with AAV-LOXL2-conditioned media.

Conclusion: These findings emphasize the therapeutic potential of LOXL2-modulated DPSC secretome in reducing inflammation and promoting chondrocyte protection. This research further underscores the importance of DPSCs, an endodontic tissue source, in advancing regenerative medicine.