Clinical rheumatology · 2025
Fire needling acupuncture attenuates synovial inflammation and cartilage degeneration in knee osteoarthritis via SDF-1/CXCR4-mediated macrophage polarization.
СтатьяНазвание и аннотация: Перевод в очереди
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Wei Jiangyan, Yang Xin, Zhao Luopeng, Liu Xueyan, Ge Xiaobo, Zhang Jiarun, Zhou Jun, Zhang Chengcheng, Song Yine, Li Wenshan, Yuan Fang, Wang Yizhan, Liu Lu, Li Bin
Аннотация
OBJECTIVES: This study aims to investigate the molecular mechanisms underlying the therapeutic effects of fire needling acupuncture (FNA) in alleviating knee osteoarthritis (KOA) symptoms, focusing on the SDF-1/CXCR4 signaling pathway and macrophage polarization.
METHODS: A KOA mouse model was established using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT + DMM) surgery. After four weeks, FNA was administered twice weekly for another four weeks. Pain behavior was assessed via weight-bearing and mechanical withdrawal thresholds. Micro-CT, histological staining, immunohistochemistry, and immunofluorescence were utilized to evaluate cartilage and subchondral bone changes, along with relevant markers. Synovial inflammation and macrophage polarization were analyzed, specifically targeting the SDF-1/CXCR4 pathway. The effects of CXCR4 modulation were assessed using AMD3100 (antagonist) and ATI-2341 (agonist).
RESULTS: FNA treatment improved joint function, reduced pain, alleviated synovial inflammation, and mitigated subchondral bone changes. It decreased cartilage damage while upregulating COL2 and SOX9, and downregulating MMP13. The SDF-1/CXCR4 pathway was activated, leading to a shift in macrophage polarization characterized by reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and increased anti-inflammatory cytokine IL-10. M0 macrophage marker F4/80 and M1 marker CD86 were downregulated, whereas M2 marker CD206 was upregulated. The ATI-2341 group exhibited therapeutic effects similar to FNA, while the AMD3100 and AMD3100 + FNA groups showed reduced efficacy.
CONCLUSIONS: FNA alleviates KOA by activating the SDF-1/CXCR4 pathway, modulating macrophage polarization, and reducing cartilage damage and inflammation. These findings highlight the therapeutic potential of FNA in the management of KOA. Key Points • Fire needling acupuncture (FNA) differentially regulates SDF-1/CXCR4 signaling in knee osteoarthritis (KOA), where synovial/cartilaginous upregulation enhances mesenchymal stem cell (MSC) homing to potentiate tissue repair, while subchondral suppression mitigates pathological bone remodeling. • FNA activates the JAK1/STAT6/PPAR-γ axis to drive macrophage phenotypic switching from pro-inflammatory M1 to anti-inflammatory M2 states, thereby preserving cartilage matrix integrity through reduced collagenase activity. • Combinatorial CXCR4 inhibition/agonist studies demonstrate FNA's targetable effects across tissue compartments, providing a mechanistic framework to refine acupuncture-based regenerative strategies. • This work establishes a precision medicine framework for degenerative joint diseases by bridging traditional acupuncture with immunomodulatory biologics to target immune-microenvironment crosstalk.
METHODS: A KOA mouse model was established using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT + DMM) surgery. After four weeks, FNA was administered twice weekly for another four weeks. Pain behavior was assessed via weight-bearing and mechanical withdrawal thresholds. Micro-CT, histological staining, immunohistochemistry, and immunofluorescence were utilized to evaluate cartilage and subchondral bone changes, along with relevant markers. Synovial inflammation and macrophage polarization were analyzed, specifically targeting the SDF-1/CXCR4 pathway. The effects of CXCR4 modulation were assessed using AMD3100 (antagonist) and ATI-2341 (agonist).
RESULTS: FNA treatment improved joint function, reduced pain, alleviated synovial inflammation, and mitigated subchondral bone changes. It decreased cartilage damage while upregulating COL2 and SOX9, and downregulating MMP13. The SDF-1/CXCR4 pathway was activated, leading to a shift in macrophage polarization characterized by reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and increased anti-inflammatory cytokine IL-10. M0 macrophage marker F4/80 and M1 marker CD86 were downregulated, whereas M2 marker CD206 was upregulated. The ATI-2341 group exhibited therapeutic effects similar to FNA, while the AMD3100 and AMD3100 + FNA groups showed reduced efficacy.
CONCLUSIONS: FNA alleviates KOA by activating the SDF-1/CXCR4 pathway, modulating macrophage polarization, and reducing cartilage damage and inflammation. These findings highlight the therapeutic potential of FNA in the management of KOA. Key Points • Fire needling acupuncture (FNA) differentially regulates SDF-1/CXCR4 signaling in knee osteoarthritis (KOA), where synovial/cartilaginous upregulation enhances mesenchymal stem cell (MSC) homing to potentiate tissue repair, while subchondral suppression mitigates pathological bone remodeling. • FNA activates the JAK1/STAT6/PPAR-γ axis to drive macrophage phenotypic switching from pro-inflammatory M1 to anti-inflammatory M2 states, thereby preserving cartilage matrix integrity through reduced collagenase activity. • Combinatorial CXCR4 inhibition/agonist studies demonstrate FNA's targetable effects across tissue compartments, providing a mechanistic framework to refine acupuncture-based regenerative strategies. • This work establishes a precision medicine framework for degenerative joint diseases by bridging traditional acupuncture with immunomodulatory biologics to target immune-microenvironment crosstalk.