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

Background/Aim: Osteoarthritis (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. Methods: CD4(+) 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 (ROR gamma t) expression was determined in cells and mice, accompanied by the mea-surement of the proportion of Th17 and Treg cells and the levels of interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and interferon (INF)-gamma. Articular cartilage histopathology was observed by hematoxylin and eosin staining and Safranin O-Fast Green staining. Relationship between MXI1 and TCTN2 was assessed. Results: Bioinformatics analysis identified MXI1 and TCTN2 upregulation in OA patients. Mechanistically, MXI1 bound to TCTN2 promoter to promote its transcription. Upregulated MXI1 boosted INF-gamma, STAT3, IL-1 beta, TNF-alpha, and ROR gamma t 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-1 beta, STAT3, TNF-alpha, Foxp3, INF-gamma, and ROR gamma t expression were further validated in OA mice, accompanied by aggravated articular cartilage degeneration. Conclusion: Conclusively, MXI1 facilitated Th17/Treg imbalance to accelerate OA progression.

Automated summary

This study elucidated the mechanism underlying Th17/Treg imbalance during osteoarthritis progression. The results showed that MXI1 promoted Th17 cell differentiation and restricted Treg cell differentiation, leading to accelerated progression of osteoarthritis.