Acupotomy Regulates the RIC8A/P38 MAPK Axis Based on the CircRNA Scaffold to Promote Cartilage Repair in Knee Osteoarthritis

Abstract

Knee osteoarthritis (KOA) is characterized by progressive cartilage degeneration and inflammation. This study investigated the therapeutic effects of acupotomy in a rabbit model of KOA and its association with the circular RNA phosphodiesterase 4B (circPDE4B)/resistance to inhibitors of cholinesterase 8A (RIC8A)/p38 mitogen-activated protein kinase (MAPK) signaling axis. Fifty New Zealand White rabbits were randomly assigned to five groups (n = 10 per group): control, KOA model, celecoxib, acupotomy, and sham acupotomy. KOA was induced using the modified Videman method. Beginning 6 weeks after modeling, acupotomy was administered once weekly for 4 weeks, whereas celecoxib was administered daily by gavage at 24 mg/kg for 4 weeks. Knee swelling and cartilage histopathology were evaluated. Levels of interleukin-1β (IL-1β) , tumor necrosis factor-α (TNF-α) , and interleukin-6 (IL-6) in cartilage tissue homogenates were measured by enzyme-linked immunosorbent assay. Gene and protein expression associated with cartilage metabolism and the circPDE4B/RIC8A/p38 MAPK axis were assessed by quantitative reverse transcription polymerase chain reaction and Western blotting. Compared with the KOA model group, acupotomy reduced knee swelling, improved histopathological scores, decreased inflammatory cytokine levels, downregulated matrix metalloproteinase-3 (MMP-3) , matrix metalloproteinase-13 (MMP-13), RIC8A, and phosphorylated p38 MAPK, and upregulated SRY-box transcription factor 9 (SOX9), aggrecan, and relative circPDE4B. Its effects were comparable to those of celecoxib, whereas sham acupotomy produced no significant improvement. These findings indicate that acupotomy alleviates inflammation and cartilage degeneration in rabbit KOA and is associated with modulation of the circPDE4B/RIC8A/p38 MAPK axis.