Key Takeaways & Executive Findings
- •• Electroacupuncture significantly alleviates early synovial inflammation in a rat model of knee osteoarthritis, as evidenced by improved cartilage surface and reduced Mankin's score. • Transcriptomic analysis identified 48 differentially expressed genes in synovial tissue, with 29 upregulated and 19 downregulated in response to electroacupuncture. • Key pathways involved include cell adhesion molecules, PI3K-Akt signaling, NF-κB signaling, and PPAR signaling, suggesting multiple mechanisms of action. • Electroacupuncture modulates the expression of Myh9, Hmox1, S100a8, Rack1, and Ddit3, which may serve as potential therapeutic targets.
Abstract
BACKGROUND: Early synovial inflammation plays a crucial role in the onset and progression of knee osteoarthritis and has become a significant focus for research and intervention in joint diseases. Electroacupuncture, as a common physical intervention, lacks systematic molecular-level elucidation of its mechanism on the synovium. Combining transcriptomic technology to analyze the gene expression profile of synovial tissue can help reveal key signaling pathways and targets regulated by electroacupuncture, providing theoretical basis and data support for early intervention in osteoarthritis. OBJECTIVE: To investigate the effect of electroacupuncture on early synovial inflammation in a rat model of knee osteoarthritis based on transcriptomic sequencing technology. METHODS: Twenty-four 3-month-old male Sprague-Dawley rats were randomly divided into control, model, and electroacupuncture groups (n=8 per group). The model and electroacupuncture groups underwent anterior cruciate ligament transection to induce knee osteoarthritis, while the control group did not. Four weeks after modeling, the electroacupuncture group received electroacupuncture at bilateral "Zusanli" (ST36), "Xuehai" (SP10), "Taixi" (KI3), and "Yanglingquan" (GB34) with dense-disperse waves of 3 Hz/15 Hz, current intensity 1 mA, 30 minutes per session, once daily, 5 days per week, for 2 weeks. After intervention, left knee synovium was collected for mRNA sequencing, and right knee joints were subjected to safranin O-fast green staining and Mankin's scoring. RESULTS AND CONCLUSION: (1) Compared with the control group, the model group showed rough cartilage surface and disordered synovial cell arrangement, with increased Mankin's score (P < 0.001). Compared with the model group, the electroacupuncture group showed smoother cartilage surface, reduced inflammatory infiltration in synovial tissue, and decreased Mankin's score (P < 0.05). (2) There were 29 genes upregulated in the model group and downregulated in the electroacupuncture group, and 19 genes downregulated in the model group and upregulated in the electroacupuncture group. (3) Gene Ontology analysis showed that these differentially expressed genes were mainly enriched in MHC protein complex binding, protein homodimerization activity, and BH3 domain binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed enrichment in cell adhesion molecules, phosphatidylinositol 3-kinase-protein kinase B signaling pathway, nuclear factor κB signaling pathway, and peroxisome proliferator-activated receptor signaling pathway. (4) Compared with the control group, the model group showed significantly increased mRNA expression of Myh9, Hmox1, and S100a8 (P < 0.001, P < 0.001, P < 0.001), and significantly decreased mRNA expression of Rack1 and Ddit3 (P < 0.01, P < 0.001). Compared with the model group, the electroacupuncture group showed significantly decreased mRNA expression of Myh9, Hmox1, and S100a8 (P < 0.05, P < 0.001, P < 0.001), and significantly increased Ddit3 mRNA expression (P < 0.001), while Rack1 mRNA expression showed an increasing trend but without significant difference (P > 0.05). Real-time quantitative PCR results were basically consistent with gene sequencing results. These findings indicate that electroacupuncture can significantly alleviate early synovial inflammation in knee osteoarthritis rats, possibly by inhibiting the expression of Myh9, Hmox1, and S100a8, and promoting the expression of Rack1 and Ddit3 in synovial tissue.
1. Introduction
Osteoarthritis is a degenerative disease affecting joints and surrounding soft tissues, characterized by joint pain, stiffness, and dysfunction, severely impacting patients' quality of life. The pathological mechanisms are complex, involving cartilage degeneration, subchondral bone remodeling, and synovial inflammation, with the latter gaining increasing attention. Studies have shown that synovial inflammation persists throughout the course of osteoarthritis and may even appear before obvious radiological changes. Pathological features of osteoarthritic synovium include synovial cell proliferation, inflammatory cell infiltration, fibrosis, and angiogenesis, which may contribute to pain and swelling, accelerating cartilage damage and functional decline. Therefore, early identification and effective suppression of synovitis are crucial strategies to control osteoarthritis progression.
Current clinical treatments for osteoarthritis include nonsteroidal anti-inflammatory drugs, physical therapy, and surgical intervention. However, long-term use of NSAIDs may cause gastrointestinal and cardiovascular adverse effects, while surgery is suitable for advanced stages, failing to meet the needs of early patients for safe and effective treatments. Electroacupuncture, as a safe and effective traditional therapy, has been widely used clinically, showing good analgesic and anti-inflammatory effects and improving lower limb function. Additionally, electroacupuncture can improve local microcirculation and alleviate cartilage hypoxia, suggesting that it may act through multiple mechanisms. However, the specific mechanism of electroacupuncture on early synovial inflammation in knee osteoarthritis remains unclear.
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Wen Xing, Li Mengmeng, Jia Feiyang, Qu Mengjian, Sun Guanghua, Liu Jing, Huang Xiarong, Zhong Peirui, Wang Jinling, Zhou Jun (2026). Transcriptomic analysis of the mechanism of electroacupuncture in alleviating early synovial inflammation in a rat model of knee osteoarthritis. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21582
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Frequently Asked Questions
What is the main finding of this study?
The study demonstrates that electroacupuncture significantly alleviates early synovial inflammation in a rat model of knee osteoarthritis, possibly by modulating the expression of specific genes such as Myh9, Hmox1, S100a8, Rack1, and Ddit3.
How was the knee osteoarthritis model induced in rats?
The model was induced by anterior cruciate ligament transection (ACLT) in 3-month-old male Sprague-Dawley rats.
What are the key signaling pathways affected by electroacupuncture?
The study identified enrichment in cell adhesion molecules, PI3K-Akt signaling, NF-κB signaling, and PPAR signaling pathways, suggesting these are involved in the therapeutic effect.
What is the significance of the differentially expressed genes?
The differentially expressed genes, including Myh9, Hmox1, S100a8, Rack1, and Ddit3, may serve as potential therapeutic targets for early intervention in knee osteoarthritis.
What are the clinical implications of this research?
The findings provide molecular-level evidence supporting the use of electroacupuncture as an effective early intervention for knee osteoarthritis, potentially guiding future clinical applications and drug development.
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