TNF-alpha stimulation increases dental pulp stem cell migration in vitro through integrin alpha-6 subunit upregulation. (March 2017)

• Record Type: Journal Article
• Authors: Shi, Lei; Fu, Shanqi; Fahim, Sidra; Pan, Shuang; Lina, He; Mu, Xiaodan; Niu, Yumei
• Is Part Of: Archives of oral biology. Volume 75(2017)
• Page Start: 48
• Page End: 54
• Publication Date: 2017-03
• Subjects: Cytokine -- Migration -- TNF-α -- Integrin α6 -- Dental pulp stem cell -- Regeneration; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2016.12.005
• Languages: English
• ISSNs: 0003-9969

Abstract

Highlights: Tumor necrosis factor-α (TNF-a) plays a role in migration of human dental pulp stem cells. TNF-α at a concentration of 50 ng/ml enhances hDPSC migration in vitro. Intgerin α6 expression plays a role in chemotactic migration of TNF-α treated cells. SiRNA treatment for reducing integrin α6 expression in hDPSCs causes a decrease in their migration potential and the cells lose their sense of directionality. Cytoskeletal changes in TNF-α treated group of cells are in line with the migratory phenotype in hDPSCs. Abstract: Objective: The dissemination of stem cells into tissues requiring inflammatory and reparative response is fundamentally dependent upon their chemotactic migration. Expression of TNF-α is up regulated in inflamed pulps. Dental pulp cells are also known to express integrin α6 subunit. Expression of integrin subunit α6 has been linked to the acquisition of migratory potential in a wide variety of cell types in both pathological and physiological capacities. Therefore, in this study we examined the effects of a pleiotropic cytokine TNF-α on the migration of hDPSCs and investigated its relationship with expression of integrin α6 in hDPSCs during chemotactic migration. Design: hDPSC cultures were established. Protein expression profile of α6 integrin subunit was determined. Effect of exogenous TNF-α (50 ng/ mL) on hDPSCs' migration potential was evaluated by transwell inserts and in vitro scratch assay. Upregulation/downregulation of TNF-α mediated migration was assayed in presence/absence of integrin α6 respectively. To suppress integrin α6 expression, cells were transfected with integrin α6 siRNA and then cell migration and cytoskeletal changes were evaluated. Results: Our results showed significant increase of hDPSCs' migration after stimulation with TNF-α. By knockdown of integrin α6, which is upregulated by TNF-α, we observed a decrease in the TNF-α directed chemotaxis of hDPSCs. Conclusion: In this study, we show that activation of integrin α6 brought about by TNF-α led to an increase in migratory activity in DPSCs in vitro thus describing a novel association between a cytokine TNF-α and α6 chain of an adhesion receptor integrin in regulating migration of hDPSCs.