Carnosine Prevents Type 2 Diabetes-Induced Osteoarthritis Through the ROS/NF-κB Pathway

The anti-inflammatory and antioxidant capacity of carnosine (CAR) has been investigated in autoimmune diseases. The

These findings indicate that oral CAR had chondroprotective effects on T2DM-induced OA through the reactive oxygen species (ROS)/NF-κB pathway.

Seventy male Sprague-Dawley rats were randomly divided into the control group (CG, n = 10) and the T2DM group (n = 60). A rat model of T2DM was established using a high fat diet and streptozotocin (30 mg/kg, i.p.). The 41 rats that developed T2DM were chosen and randomly divided into four groups: T2DM-induced OA group (OAG, n = 11), and the T2DM-induced OA with low, moderate, and high-doses of CAR for 8 weeks group (CAR-L, CAR-M, and CAR-H, n = 10). After 13 weeks, all rats were evaluated by enzyme-linked immunosorbent assay (ELISA), histology, immunohistochemistry, and western blotting. Fibroblast-like synoviocytes (FLSs) were obtained from the knee joints of all rats. The effects of CAR on the inflammatory response in interleukin (IL)-1β-stimulated FLSs under a high glucose environment were evaluated by real-time quantitative polymerase chain reaction, western blotting, flow cytometry, and immunofluorescence.

The results of ELISA (IL-1β and tumor necrosis factor-α), the histological evaluation (Mankin and OARSI score), western blotting [COL2A1, matrix metalloproteinase (MMP)-3, MMP-13, IL-1β, and nuclear factor-kappaB (NF-κB) p65], and immunohistochemistry (COL2A1, MMP-3, and MMP-13) indicated that oral CAR attenuated the development of T2DM-induced OA and suppressed the inflammatory response. Moreover, CAR alleviated MMP-3 and MMP-13 expression levels by decreasing reactive oxygen species content and suppressing nuclear translocation of NF-κB p65 on IL-1β-induced FLSs in a high glucose environment.