Dual effects of 1α,25-dihydroxyvitamin D3 on inflammation and osteogenic differentiation in lipopolysaccharide-stimulated dental pulp stem cells

Authors

• Seong Eun Song, Dental and Life Science Institute, Pusan National University, School of Dentistry, Yangsan, Republic of Korea
• Giyoung Yun, Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital, Dental Research Institute, Yangsan, Republic of Korea
• Cheul-Hong Kim, Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital, Dental Research Institute, Yangsan, Republic of Korea; Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Dental and Life Science Institute, Pusan National University, Yangsan, Republic of Korea
• Ji-Young Yoon, Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital, Dental Research Institute, Yangsan, Republic of Korea; Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Dental and Life Science Institute, Pusan National University, Yangsan, Republic of Korea
• Hee Young Kim, Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
• Hyae Jin Kim, Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; Department of Anesthesia and Pain Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
• Eun-Jung Kim, Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital, Dental Research Institute, Yangsan, Republic of Korea; Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Dental and Life Science Institute, Pusan National University, Yangsan, Republic of Korea

DOI

https://doi.org/10.1016/j.jds.2025.11.023

Abstract

Background/purpose

Vitamin D is traditionally known for bone metabolism and also exerts immunomodulatory effects. Dental pulp stem cells (DPSCs) are essential for pulp repair but are impaired under lipopolysaccharide (LPS)-induced inflammation. Therefore, we examined the dual effects of 1α,25-dihydroxyvitamin D₃ (1α,25(OH)₂D₃) on inflammation and osteogenic differentiation in DPSCs.

Materials and methods

Human DPSCs were pretreated with 1α,25(OH)₂D₃ (0.001–1 μM) and stimulated with LPS (1 μg/mL). Thereafter, cell viability was assessed using the 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide assay. Expression of interleukin (IL)-1β, IL-8, and cyclooxygenase-2 (COX-2) was measured using real-time quantitative PCR and Western blot. Moreover, osteogenic activity was evaluated via alkaline phosphatase (ALP) staining. Mitogen-activated protein kinase signaling was analyzed via Western blot, and extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) inhibitors were applied to confirm mechanistic involvement.

Results

The 1α,25(OH)₂D₃ did not affect DPSC viability under inflammatory conditions. However, the compound markedly suppressed LPS-induced IL-8 and COX-2 expression, with modest effects on IL-1β. LPS markedly reduced ALP activity, which was dose-dependently restored by 1α,25(OH)₂D₃. Mechanistically, 1α,25(OH)₂D₃ induced transient phosphorylation of ERK and JNK but not that of p38. Furthermore, Inhibition of ERK or JNK abrogated the osteogenic rescue, thereby confirming their essential roles.

Conclusion

The 1α,25(OH)₂D₃ exerts dual actions in LPS-stimulated DPSCs by attenuating inflammatory mediators and promoting osteogenic differentiation through ERK/JNK signaling. These findings suggest its promising potential as a therapeutic adjunct in regenerative endodontics under inflamed conditions.

Recommended Citation

Song, Seong Eun; Yun, Giyoung; Kim, Cheul-Hong; Yoon, Ji-Young; Kim, Hee Young; Kim, Hyae Jin; and Kim, Eun-Jung, "Dual effects of 1α,25-dihydroxyvitamin D3 on inflammation and osteogenic differentiation in lipopolysaccharide-stimulated dental pulp stem cells" (2026). Articles in Press. 2.
https://jds.ads.org.tw/articles_in_press/2