Melatonin attenuates dental pulp stem cells senescence due to vitro expansion via inhibiting MMP3.

Autor: Zhang Z; Department of Endodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, China., Bao Y; Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China., Wei P; Department of Endodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, China., Yan X; Department of Endodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, China., Qiu Q; Department of Endodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, China., Qiu L; Department of Endodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang, China.
Jazyk: angličtina
Zdroj: Oral diseases [Oral Dis] 2024 May; Vol. 30 (4), pp. 2410-2424. Date of Electronic Publication: 2023 Jul 14.
DOI: 10.1111/odi.14649
Abstrakt: Objective: We aimed to identify the crucial genes involved in dental pulp stem cell (DPSC) senescence and evaluate the impact of melatonin on DPSC senescence.
Methods: Western blotting, SA-β-Gal staining and ALP staining were used to evaluate the senescence and differentiation potential of DPSCs. The optimal concentration of melatonin was determined using the CCK-8 assay. Differentially expressed genes (DEGs) involved in DPSC senescence were obtained via bioinformatics analysis, followed by RT-qPCR. Gain- and loss-of-function studies were conducted to explore the role of MMP3 in DPSC in vitro expansion and in response to melatonin. GSEA was employed to analyse MMP3-related pathways in cellular senescence.
Results: Treatment with 0.1 μM melatonin attenuated cellular senescence and differentiation potential suppression in DPSCs due to long-term in vitro expansion. MMP3 was a crucial gene in senescence, as confirmed by bioinformatics analysis, RT-qPCR and Western blotting. Furthermore, gain- and loss-of-function studies revealed that MMP3 played a regulatory role in cellular senescence. Rescue assays showed that overexpression of MMP3 reversed the effect of melatonin on senescence. GSEA revealed that the MMP3-dependent anti-senescence effect of melatonin was associated with the IL6-JAK-STAT3, TNF-α-Signalling-VIA-NF-κB, COMPLEMENT, NOTCH Signalling and PI3K-AKT-mTOR pathways.
Conclusion: Melatonin attenuated DPSC senescence caused by long-term expansion by inhibiting MMP3.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: