Reversing Microglial Polarisation by High Intensity Interval Training: A Novel Approach to Mitigate Inflammatory Responses in Osteoarthritis via Jak2/Stat3 Pathway.

Abstract

Osteoarthritis (OA) is associated with inflammatory responses linked to microglial polarisation within the central nervous system. However, exploring therapeutic approaches and their underlying mechanisms remains a direction for future research. The present study investigates the potential of high-intensity interval training (HIIT) to alleviate inflammation and facilitate the shift from M1 to M2 microglial polarisation via the Jak2/Stat3 pathway in an OA rat model. Wistar rats were induced with OA via intra-articular injection of monosodium iodoacetate and subsequently underwent HIIT for six consecutive weeks after a 4-week establishment period. Pain thresholds were measured using the von Frey test. Immunofluorescence detected Tmem119, SP, Glu, c-Fos, and IL-6, while flow cytometry analysed CD68 and CD163 levels. Proteomics compared the protein differences between the OA and HIIT groups. The Jak2/Stat3 pathway was activated in OA rats with C-A1 injections, followed by HIIT and subsequent Western blot analysis of inflammatory cytokines. The results indicated a significant decrease in pain threshold from the third to the tenth week in OA rats, while HIIT was found to increase pain thresholds. HIIT was found to promote M1 to M2 microglial polarisation and downregulate the expression of Tmem119, SP, Glu, c-Fos, and IL-6. Additionally, HIIT was more effective in suppressing Jak2 and Stat3 expression levels compared to OA rats. Activation of the Jak2/Stat3 pathway significantly increased the expression of Glu, c-fos, SP, and IL-6, but HIIT reversed these OA-induced increases. Compared to the OA + C-A1 group, the expression levels of Glu, c-fos, SP, and IL-6 were significantly reduced in the OA + C-A1 + HIIT group. In conclusion, HIIT effectively mitigates OA-induced inflammatory responses by reversing microglial polarisation through the Jak2/Stat3 pathway.