Moxibustion Regulates the Imbalance of Cartilage Degradation and Repair in Knee Osteoarthritis Rabbits via the SDF-1/CXCR4 Axis: Is Stimulating Heat-Sensitized Acupoints More Efficacious?

Background: This study investigated whether moxibustion, particularly at heat-sensitized acupoints, exerts therapeutic effects on knee osteoarthritis (KOA) and whether these effects are associated with the modulation of the SDF-1/CXCR4 signaling axis, a key regulator of cartilage metabolism. Methods: A KOA model was induced in rabbits, which were then randomized into control (n=6), model (n=6), and moxibustion groups. Following a 14-day moxibustion intervention, the moxibustion group was further classified into heat-sensitive moxibustion (HSM, n=6) and non-heat-sensitive moxibustion (NSM, n=6) subgroups based on thermal response measured by infrared thermal imaging. Heat-sensitization was defined as a sustained distal skin temperature elevation ≥ 1°C during treatment, while non-heat-sensitive was defined as an elevation < 1°C. After a 14-day intervention, outcomes were assessed via the Lequesne MG index, histopathology, RT-qPCR, Western blot, and Micro-CT. Results: Compared to the model group (Lequesne score: 9.667±1.633), both HSM (3.167±0.753, p<0.01) and NSM (5.000±0.894, p<0.01) significantly improved joint function. HSM significantly outperformed NSM (p<0.05). At the molecular level, HSM significantly downregulated SDF-1 (1.570±0.131 vs 1.957±0.301, p<0.05), CXCR4 (1.902±0.318 vs 2.313±0.277, p<0.05), and MMP-13 (2.166±0.312 vs 2.608±0.340, p<0.05) mRNA expression, while significantly upregulating SOX9 (0.774±0.086 vs 0.638±0.089, p<0.05) and Col2a1 (0.728±0.091 vs 0.601±0.078, p<0.05) compared to NSM. In terms of subchondral bone, although both moxibustion groups showed significant improvements over the model group (all p<0.05), no statistically significant differences were observed between HSM and NSM for BMD, BV/TV, Tb.N, Tb.Th, or Tb.Sp (all p>0.05). Conclusion: Moxibustion ameliorates KOA, and this effect is accompanied by the suppression of the SDF-1/CXCR4 signaling axis and restoration of the balance between cartilage catabolism and anabolism. Stimulation of heat-sensitized acupoints offers superior benefits for functional recovery and molecular markers of cartilage repair compared to non-heat-sensitive acupoints, although this advantage was not observed in subchondral bone parameters.