Summary

Knee osteoarthritis (KOA) can be treated with the Japanese traditional Kampo medicine, Boiogito (BOT), however, the details of its therapeutic effects remain unclear. This study assessed the preventive effect of BOT and clarified that BOT significantly inhibits osteophyte formation associated with KOA development induced by meniscus destabilization.

Abstract

Knee osteoarthritis (KOA) is a chronic joint disease that predominantly affects middle-aged and elderly individuals, and its prevalence is continuously increasing. KOA patients often experience knee swelling, pain, and walking difficulty, which can significantly impact their daily lives. Although surgery can alleviate symptoms in severe KOA, no preventive treatments have been established to halt disease progression. Boiogito (BOT), a traditional Japanese herbal medicine which consists of 6 herbal ingredients, has demonstrated clinical effectiveness in managing knee swelling, pain, and joint effusion. Our study investigated the effects of BOT in a rat model of KOA.

We induced KOA in the right knees of 10-week-old male Wistar rats using a procedure known as destabilization of the medial meniscus (DMM). BOT extract powder was mixed into the rats' powder chow at a concentration of 1% (w/w). The rats were divided into four groups and observed for 12 weeks (n=3 for each group): ① Control group (no surgical procedure), ② Sham group (meniscus exposed but not destabilized), ③ DMM group (meniscus exposed and destabilized), and ④ DMM + BOT group (KOA induced and treated with 1% BOT). After 12 weeks, CT scans of the right knees were performed, and the knee joints were harvested for histological analysis with toluidine blue. The severity of KOA was assessed and compared using the Osteoarthritis Research Society International (OARSI) score.

CT imaging of the right knee joints showed that the medial meniscus deviated related to the medial edge of the tibial joint surface approximately 80% in both the DMM and DMM + BOT groups (79.5 ± 35.6% and 82.3 ± 15.4%, respectively), while the Control and Sham group did not show meniscus extrusion (4.3 ± 7.5% points and 9.4 ± 8.2% points, respectively), confirming that the DMM rat model was appropriately created. The DMM group had a significantly higher OARSI score (9.0 ± 2.1 points) compared to the Control (0 points) and Sham (2.0 ± 3.5 points) group, while the DMM + BOT group had a significantly lower score (2.9 ± 0.8 points) than the DMM group. Further analysis of OARSI score components—cartilage degradation, subchondral bone damage, and osteophyte formation—revealed that only osteophyte formation was significantly reduced in the DMM + BOT group (2.5 ± 0.5 points, 0 points, and 0.4 ± 0.3 points, respectively) compared to the DMM group (6.1 ± 2.5 points, 1.5 ± 0.5 points, and 1.3 ± 0.6 points, respectively).

Osteophyte formation promotes meniscal extrusion and increases the load pressure on joint cartilage and subchondral bone, making it a crucial factor in the further progression of KOA. Our results indicate that oral administration of BOT can suppress osteophyte formation, suggesting that this herbal medicine may help prevent KOA progression. However, the exact mechanism by which BOT inhibits osteophyte formation remains unclear, and further research is needed to explore the underlying molecular mechanisms.