Max interacting protein 1 induces IL-17-producing T helper/regulatory T imbalance in osteoarthritis by upregulating tectonic family member 2

Abstract

Background/AimOsteoarthritis (OA) is a common total joint disorder associated with regulatory T cell (Treg)/IL-17-producing T helper (Th17) cell imbalance. This study elucidated the mechanism underlying Th17/Treg imbalance during OA progression. MethodsCD4+ T cells were isolated and induced to differentiate and obtain Th17 and Treg cells, and an OA mouse model was established by anterior cruciate ligament transection surgery, followed by loss- and gain-of-function assays. Max interacting protein 1 (MXI1), tectonic family member 2 (TCTN2), Forkhead Box Protein P3 (Foxp3), signal transducer and activator of transcription 3 (STAT3), and retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt) expression was determined in cells and mice, accompanied by the measurement of the proportion of Th17 and Treg cells and the levels of interleukin (IL)− 1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ. Articular cartilage histopathology was observed by hematoxylin and eosin staining and Safranin O-Fast Green staining. Relationship between MXI1 and TCTN2 was assessed. ResultsBioinformatics analysis identified MXI1 and TCTN2 upregulation in OA patients. Mechanistically, MXI1 bound to TCTN2 promoter to promote its transcription. Upregulated MXI1 boosted INF-γ, STAT3, IL-1β, TNF-α, and RORγt levels and Th17 cell differentiation, but restricted Foxp3 expression and Treg cell differentiation in CD4+ T cells. Effects caused by overexpressed MXI1 were negated by silenced TCTN2. Also, the impacts of MXI1 overexpression on Th17/Treg imbalance and IL-1β, STAT3, TNF-α, Foxp3, INF-γ, and RORγt expression were further validated in OA mice, accompanied by aggravated articular cartilage degeneration. ConclusionConclusively, MXI1 facilitated Th17/Treg imbalance to accelerate OA progression.