Adipose-derived mesenchymal stem cell injection into the KI10 acupoint mitigates cartilage damage in KOA rats through PGE2-mediated α7nAChR/NF-κB pathway

Abstract

Background

Knee osteoarthritis (KOA) is a chronic joint disorder. Current treatment options offer limited benefit. Adipose-derived mesenchymal stem cells (ADSCs), known for their chondrogenic potential and anti-inflammatory and immunomodulatory functions, have gained growing interest in regenerative therapy. Acupoint interventions are widely recognized for analgesic and anti-inflammatory effects. Combining ADSCs with acupoint-targeted delivery may represent a novel therapeutic approach. This study evaluated the therapeutic efficacy and underlying mechanisms of ADSC injection into the KI10 acupoint in mitigating KOA-related cartilage damage.

Methods

KOA models were established in male Sprague–Dawley rats, followed by ADSC injection into the KI10 acupoint. Pain, motor function, and joint structural changes were assessed through ethological testing, imaging, histopathology, transmission electron microscopy, and molecular analyses. TMT-based proteomics was used to identify mechanistic pathways, and the α7nAChR antagonist methyllycaconitine citrate (MLA) was used to validate the pathways.

Results

ADSC injection into the KI10 acupoint significantly reduced pain and improved motor performance in KOA rats. Imaging and histological analysis revealed significant decreases in synovial inflammation and cartilage degeneration. Transmission electron microscopy confirmed diminished chondrocyte injury. Proteomic analysis indicated activation of the cholinergic anti-inflammatory pathway, and MLA administration reversed these therapeutic benefits, verifying pathway involvement.

Conclusions

ADSC injection into the KI10 acupoint effectively attenuates cartilage injury and inflammation in KOA by activating the PGE2-mediated α7nAChR/NF-κB signaling pathway. This combined strategy harnesses the complementary advantages of stem cell therapy and acupoint-targeted intervention, offering a promising therapeutic avenue for KOA.