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PublicationThe Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing(2018-03-14) Kou, Xiaoxing; Xu, Xingtian; Chen, Chider; Sanmillan, Maria Laura; Cai, Tao; Zhou, Yanheng; Girauda, Claudio; Le, Anh; Shi, SongtaoMesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-Associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs. Moreover, we reveal that MSCs produce and secrete interleukin-1 receptor antagonist (IL-1RA) associated with sEVs to maintain rapid wound healing in the gingiva via the Fas/Fap-1/Cav-1 cascade. Tumor necrosis factor-? (TNF-?) serves as an activator to up-regulate Fas and Fap-1 expression via the nuclear factor ?B pathway to promote IL-1RA release. This study identifies a previously unknown Fas/Fap-1/Cav-1 axis that regulates SNARE-mediated sEV and IL-1RA secretion in stem cells, which contributes to accelerated wound healing. © 2018 The Authors, Some Rights Reserved. PublicationThe Role of IL-6 in Osteogenic and Neurogenic Differentiation Potentials of Dental Pulp Stem Cells (DPSCs)(2019-06-30) Park, YongTae; Kou, Xiaoxing; Shi, SongtaoIntroduction: Interleukin 6 (IL-6) is a pleiotropic soluble mediator which is involved with many different parts of inflammatory processes. Studies have shown that there is a significantly higher concentration of IL-6 in inflamed pulp tissues when compared to healthy pulp tissues. However, there are no comprehensive studies on how IL-6 can interact with dental pulp stem cells (DPSCs) from healthy (H-DPSCs) and inflamed pulp tissues (I-DPSCs) and how it can affect the differentiation potential of DPSCs. Therefore, I hypothesized that IL-6 can promote osteogenesis while inhibiting neurogenesis from DPSCs. The aims of this study were to investigate the baseline differences between the H-DPSCs and I-DPSCs, and determine how IL-6 can affect the osteogenic and neurogenic differentiation potentials of DPSCs. Materials and Methods: H-DPSCs and I-DPSCs were isolated and cultured from 28 teeth consisting healthy impacted third molars (n=14) from patients with 17-27 years of age, and severely decayed molars (n=14) with spontaneous, sharp pain from patients with 24 – 56 years of age, respectively. The levels of IL-6 from H-DPSCs and I-DPSCs were measured by ELISA, and IL-6 and neutralizing IL-6 were added to H-DPSCs and I-DPSCs, respectively. Immunofluorescence and Alizarin Red staining, and western blot were performed to assess the differentiation potentials of DPSCs. The independent unpaired two-tailed Student’s t-test were performed following quantification analysis. Results: H-DPSCs and I-DPSCs showed similar expression of stem cell markers including CD44, CD73, CD90, and CD105, while H-DPSCs showed lower level of IL-6 (p Conclusion: This study showed IL-6 has the capacities to enhance osteogenesis while hindering neurogenesis of DPSCs.