Omentin-1 reduced synovial M1 macrophages through SIRT6 signaling pathway and alleviated knee osteoarthritis response in mice

Purpose: This study aimed to evaluate the therapeutic effects of Omentin-1 on Osteoarthritis and explore its protective mechanisms.

Methods: Two Osteoarthritis mouse models were created: wild-type and SIRT6^-/-. After five weeks of Omentin-1 injection, we evaluated M1 and M2 macrophage distribution in the mouse synovium and measured inflammatory factor levels. Matrix proteins related to cartilage repair were detected, and safranin O-green and toluidine blue staining were used to evaluate the repair. Furthermore, we evaluated how Omentin-1 regulated macrophage polarization and explored potential mechanisms.

Result: Omentin-1 was low in Osteoarthritis mice and linked to M1 macrophage polarization. It protected these mice by reducing synovial inflammation, decreasing M1 Macrophages, increasing M2 Macrophages, and lowering pro-inflammatory factors while raising anti-inflammatory factors and minimizing inflammatory cell infiltration in the synovium. Omentin-1 enhanced Collagen II and α-SMA expression in cartilage, aiding repair. Further mechanistic studies indicated that Omentin-1 can enhance the expression of SIRT6 in the joint tissues of mice with Osteoarthritis. Omentin-1's inhibition of inflammation in Osteoarthritis mice was linked to SIRT6.

Conclusion: Elevated Omentin-1 levels can mitigate the inflammatory response in Osteoarthritis by enhancing SIRT6 expression, inhibiting inflammatory factors, suppressing M1 Macrophages, and increasing M2 Macrophages.