Interleukin-17A enhances osteogenic differentiation by activating ERK/MAPK in stem cells derived from human exfoliated deciduous teeth

Introduction: Human exfoliated deciduous teeth-derived stem cells (SHEDs) have been shown as an excellent source of bone regeneration. Interleukin-17A (IL-17A) facilitates bone differentiation in various cell types, including SHEDs. In this study, we have demonstrated IL-17A's stimulating effect on SHEDs in osteogenic differentiation and further evaluated the role of the ERK/MAPK signaling pathway in this process. Methods: The function of IL-17A in osteogenic differentiation, prolifera-tive activity, and MAPK cascade activation in SHEDs were investigated. Results: IL-17A significantly enhanced proliferative and alkaline phosphatase activities in SHEDs. Furthermore, the expression levels of different osteogenic proteins including COL1A1, ALP, OPN, RUNX, and OCN were signifi-cantly elevated in IL-17A-treated SHEDs. Moreover, IL-17A triggered MAPK signaling in SHEDs, as evidenced by significant upregulation of both downstream ERK targets, P38 and JNK pathways, and upstream activators. In addition, ERK/MAPK activation time-dependently established the participa-tion of MAPK signaling in SHED osteogenic differentiation. Conclusion: These findings suggest that IL-17A-induced ERK/MAPK signaling pathway activation is necessary for SHEDs to differentiate into osteoblasts. This reiterates the significance of this particular intracellular signaling pathway in controlling SHED osteogenic differentiation, which is a promising source of bone tissue regenera-tion.