High Dose IL-17A Enhances the Antiosteoarthritic Effect of Dental Pulp Mesenchymal Stem Cells by Reducing Inflammatory Response and Promoting Chondrocyte Proliferation

Abstract Objective: Mesenchymal stem cells (MSCs) have promising potential in regenerative therapy, partially through their potent immune modulation. The inflammatory cytokine IL-17A has been suggested to improve the therapeutic efficacy of MSCs. Herein, we determined whether pretreatment of dental pulp MSCs (DPMSCs) with IL-17A enhances the therapeutic potency of DPMSCs for osteoarthritis (OA).Methods: DPMSCs pretreated with IL-17A (0-75 ng/ml) were co-cultured with T lymphocytes for cytokine assay. In a rat OA model, DPMSCs pretreated with IL-17A were evaluated for antiosteoarthritic activity. Rat knee joints were harvested for color Doppler ultrasonography and histological staining, and synovial fluid was collected for cytokine assay. Additionally, chondrocytes isolated form joint cartilage of OA rats were co-cultured with IL-17A-pretreated DPMSCs for cell proliferation assay.Results: DPMSCs demonstrated a pluripotent capacity to differentiate into osteocytes, adipocytes, and chondrocytes. For in vitro co-culture, although DPMSCs pretreated with low dose of IL-17A (25 ng/ml) had inflammation-promoting effect, indicated by increased IL-2 and TNF-α secretion and decreased IL-4 release, high dose IL-17A (75 ng/ml) pretreatment enhanced the anti-inflammatory activity of DPMSCs. In vivo, high dose IL-17A-pretreated DPMSCs showed a stronger antiosteoarthritic activity than untreated DPMSCs, indicated by significantly reducing joint swelling, synovial fluid formation, the OARSI scores, and the production of inflammatory cytokines in synovial fluid. Besides, high dose IL-17A- pretreated DPMSCs enhanced the stimulatory activity of DPMSCs in chondrocyte proliferation in vitro.Conclusion: high dose IL-17A enhances the immunosuppressive property of DPMSCs, which helps alleviate osteoarthritis by inhibiting inflammatory response and promoting chondrocyte proliferation in the affected joints.