Key Takeaways & Executive Findings
- •• A novel rat model of early knee osteoarthritis with cold-dampness obstruction syndrome was successfully established by combining anterior cruciate ligament transection with artificial cold-damp environment. • The cold-dampness obstruction group exhibited significant traditional Chinese medicine syndrome manifestations, including mental fatigue, reduced activity, loose stools, and dark purple tongue. • CatWalk gait analysis revealed significant changes in gait parameters, such as decreased paw intensity and increased swing phase, in the cold-dampness obstruction group compared to controls. • Histopathological evaluation showed higher Mankin scores in the cold-dampness obstruction group, indicating more severe cartilage degeneration, validating the model's effectiveness.
Abstract
BACKGROUND: Existing animal models of knee osteoarthritis predominantly focus on mechanical injury factors but fail to simulate and observe the "cold-dampness obstruction" syndrome characteristics in traditional Chinese medicine. OBJECTIVE: To construct a traditional Chinese medicine-Western medicine integrated knee osteoarthritis model for cold-dampness obstruction syndrome and validate its efficacy via a multidimensional assessment. METHODS: Twenty-four male Sprague-Dawley rats (SPF-grade) were randomly divided into sham-operated, model, and cold-dampness obstruction groups. The latter two groups underwent anterior cruciate ligament transection of the right hind knee. The cold-dampness obstruction group received artificial cold-damp environment intervention (temperature 10.5 °C, humidity 90%, 4 h/day, for 4 weeks) starting 14 days post-surgery. The sham-operated group had skin incision and immediate closure. Before modeling and at 1, 2 weeks post-modeling, and 4 weeks after cold-damp intervention, traditional Chinese medicine syndrome scores and CatWalk gait analysis were performed. Right hind knee joint tissues were harvested for histopathological observation and Mankin scoring. RESULTS AND CONCLUSION: (1) Traditional Chinese medicine syndrome scores: The cold-dampness obstruction group showed significant mental fatigue, reduced activity, loose stools, dark purple tongue, dull fur, decreased food intake, and slower weight gain (P < 0.01). (2) CatWalk gait parameters: At 1 week post-modeling, compared with the sham-operated group, the model and cold-dampness obstruction groups showed decreased maximum contact intensity, print length, maximum intensity, average intensity of 15 maximum pixels, and increased swing phase of the right hind paw (all P < 0.01). The cold-dampness obstruction group also showed significantly decreased swing speed (P < 0.05). After 4 weeks in the artificial climate chamber, compared with the sham-operated group, the cold-dampness obstruction group showed significantly decreased maximum contact intensity, maximum intensity, average intensity of 15 maximum pixels (P < 0.01), increased swing phase (P < 0.01), and decreased swing speed (P < 0.05). (3) Histopathology: Mankin scores in the model and cold-dampness obstruction groups were significantly higher than in the sham-operated group (P < 0.01), and the cold-dampness obstruction group had significantly higher scores than the model group (P < 0.01). These results indicate that anterior cruciate ligament transection combined with cold-damp environment can successfully construct a cold-dampness obstruction type early knee osteoarthritis rat model. CatWalk gait parameters and traditional Chinese medicine syndrome scores provide an objective evaluation system for studying the mechanisms of traditional Chinese medicine in knee osteoarthritis.
1. Introduction
Knee osteoarthritis is a chronic joint disease characterized by cartilage destruction, degeneration, and synovial inflammation. As the degenerative joint disease with the highest disability rate worldwide, pain, swelling, and movement disorders severely affect patients' quality of life, especially lower limb biomechanics [1-3]. Traditional Chinese medicine theory regards "wind, cold, and dampness pathogens" as important pathogenic factors of knee osteoarthritis, among which cold-dampness obstruction syndrome is the most common type and is the primary syndrome in guidelines [4-6].
Animal models are crucial for in-depth research on disease etiology, pathogenesis, diagnosis, and treatment. Anterior cruciate ligament transection can yield a rapid, stable, reproducible osteoarthritis model similar to humans [7-8]. Surgery-induced joint instability and inflammation cause local qi and blood stasis, resembling "stasis" and "obstruction" in traditional Chinese medicine. This "obstruction" state is highly sensitive to external cold pathogens, but there is a lack of disease-syndrome combined rat models of traditional Chinese medicine syndromes. The CatWalk gait analysis system is significant in evaluating osteoarthritis experimental studies [9-10]. Our team previously found that gait analysis can objectively reflect disease changes in clinical knee osteoarthritis patients [11]. We believe that the three-dimensional gait analysis evaluation criteria used clinically can be analogized to CatWalk gait analysis system parameters. Therefore, this study innovatively combines anterior cruciate ligament transection with artificial cold-damp environment intervention to establish a cold-dampness obstruction type early knee osteoarthritis rat model integrating traditional Chinese and Western medicine etiologies. By quantifying motor function changes with CatWalk gait analysis, combined with traditional Chinese medicine syndrome scores and histopathological examination, we evaluate the feasibility of this model, providing a key model for traditional Chinese medicine syndrome differentiation and treatment of knee osteoarthritis.
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BAI Xue, TIAN Yukui, GUO Lei, SHI Mengni, CUI Xiaofeng, WANG Cheng, LI Jingxian, ZHU Qingguang, LIU Junchang (2026). Construction of an early knee osteoarthritis rat model: CatWalk-based gait analysis and evaluation. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21317
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Frequently Asked Questions
What is the cold-dampness obstruction syndrome in traditional Chinese medicine?
Cold-dampness obstruction syndrome is a pattern in traditional Chinese medicine characterized by the invasion of cold and dampness pathogens into the body's meridians, muscles, and joints, leading to qi and blood stasis and obstruction. It manifests as cold pain, heaviness, and limited movement in the limbs and joints, and is a common type of Bi syndrome.
How was the cold-dampness obstruction type knee osteoarthritis rat model constructed?
The model was constructed by performing anterior cruciate ligament transection on the right hind knee of rats, followed by exposure to an artificial cold-damp environment (temperature 10.5 °C, humidity 90%, 4 hours daily for 4 weeks) starting 14 days post-surgery.
What is CatWalk gait analysis and why is it used?
CatWalk gait analysis is an automated system that quantitatively assesses gait parameters in rodents. It is used to objectively evaluate motor function changes in animal models of diseases like knee osteoarthritis, providing sensitive and reliable measurements of paw intensity, print length, swing phase, and other parameters.
What were the main findings of this study?
The study successfully established a cold-dampness obstruction type early knee osteoarthritis rat model. The model group showed significant traditional Chinese medicine syndrome manifestations, altered CatWalk gait parameters indicating pain and dysfunction, and higher Mankin scores reflecting cartilage degeneration, confirming the model's validity.
Why is this model important for knee osteoarthritis research?
This model integrates traditional Chinese medicine syndrome characteristics with Western medicine pathology, providing a more clinically relevant platform for studying the mechanisms of knee osteoarthritis and evaluating the efficacy of traditional Chinese medicine interventions, thereby facilitating the development of syndrome-specific treatments.
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