Early Intervention With Boiogito to Suppress Knee Osteoarthritis Progression: An Experimental Approach Using a Medial Meniscus Instability Rat Model

TL;DR

This study shows that early use of Boiogito, a traditional Japanese medicine, can slow knee osteoarthritis progression in rats by improving joint function and reducing bone and cartilage damage.

Contribution

The study demonstrates the efficacy of early Boiogito administration in preventing knee osteoarthritis progression in a rat model.

Findings

Early Boiogito treatment improved motor function and reduced cartilage degradation in rats.

Early administration lowered subchondral bone osteoclast numbers and MMP-13 levels.

Late Boiogito treatment showed limited effectiveness compared to early intervention.

Abstract

Background

Knee osteoarthritis (KOA) is a prevalent and chronic condition characterized by swelling, pain, and limited range of motion of the knee due to degenerative changes in joint structures, leading to impairment in performing daily activities. Although conservative treatments, such as exercise therapy and nonsteroidal anti-inflammatory drugs are employed, there are few effective therapeutic options for preventing disease progression. During early KOA, there is osteoclast proliferation in the subchondral bone, disruption in cartilage homeostasis, elevation of matrix metalloproteinase-13 (MMP-13) levels, and reduction in tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) levels. Boiogito (BOT), which is a traditional Japanese medicinal formula, attenuates KOA progression, however, its effects when administered after KOA progression remain unclear. This study aimed to assess the therapeutic efficacy of BOT in preventing KOA progression in a rat model by focusing on its effects on motor function, subchondral bone turnover, and cartilage degradation in relation to the timing of administration.

Methods

A rat KOA model was created by destabilizing the medial meniscus (DMM). Rats were divided into Sham, DMM, DMM + BOT (0w, BOT administered immediately post-surgery), and DMM + BOT (3w, BOT administered 3 weeks post-surgery) groups. BOT was included in the diet at 1% (w/w). Motor function was evaluated biweekly by a treadmill running test, while structural changes in the knee were assessed by measuring the medial meniscus extrusion ratio (MMER) using computed tomography (CT). Histological and immunohistochemical analyses were conducted to evaluate joint degeneration via the Osteoarthritis Research Society International (OARSI) score, osteoclast numbers in subchondral bone through tartrate-resistant acid phosphatase (TRAP) staining, and MMP-13/TIMP-1 ratios in articular cartilage.

Results

Treadmill testing revealed that the DMM + BOT (0w) had significantly higher running speeds compared with the DMM and DMM + BOT (3w) groups. In all groups that underwent DMM surgery, the MMER was not significantly different. Histological assessments showed that the DMM + BOT (0w) group had lower OARSI scores and reduced osteoclast numbers in the subchondral bone compared with the DMM group. Immunohistochemical analysis showed a significant reduction in MMP-13 expression and MMP-13/TIMP-1 ratios in the DMM + BOT (0w) group, whereas the DMM + BOT (3w) group showed limited efficacy compared with the early intervention.

Conclusion

Early administration of BOT attenuates KOA progression by preserving motor function, reducing subchondral bone turnover, and mitigating cartilage degradation. These findings highlight the importance of early intervention with BOT to achieve optimal therapeutic outcomes in KOA.

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