Acupotomy Ameliorates Articular Cartilage Fibrosis in a Rabbit Model of Knee Osteoarthritis via the TGF-β1/Smad Pathway

Longfei Xing,1,* Wenting Zhu,2,* Xilin Chen,3,4 Rui Che,5 Jiangong Wu,1 Yan Guo,6 Chuxi Liang1 1Department of Traditional Chinese Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Rehabilitation Medicine, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Acupuncture and Rehabilitation, The Fifth College of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 4Department of Acupuncture and Rehabilitation, Guangdong Second Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Acupuncture and Physiotherapy, Beijing Water Resources Hospital, Beijing, People’s Republic of China; 6Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuxi Liang, Department of Traditional Chinese Medicine, Peking University People’s Hospital, Beijing, 100029, People’s Republic of China, Tel +86-15120058248, Email [email protected]: This study aimed to investigate whether acupotomy can regulate the activity of factors related to the TGF-β 1/Smad pathway, thereby reducing the degree of cartilage fibrosis in knee osteoarthritis (KOA) and alleviating cartilage degradation.Methods: A modified Videman’s long-term knee joint immobilization method in the extended position was used to establish the KOA model. Behavioral Lequesne MG scoring was performed before and after the acupotomy intervention. Masson staining was used to observe the morphology and structure of the cartilage using light microscopy and scanning electron microscopy (SEM). Western blotting and real-time quantitative polymerase chain reaction (RT-PCR) were used to detect the protein levels and mRNA expression of Smad3, Smad7, TGF-β 1, collagen type I (Col-I), collagen type II (Col-II), and collagen type III (Col-III) in the cartilage tissue of acupotomy-treated KOA rabbits.Results: The modified Lequesne MG score was significantly higher in the KOA group than that in the control group. Histologically, the cartilage in the KOA group exhibited fissures, matrix dissolution, reduced Col-II content, and obvious fibrosis. TGF-β 1 and Smad3 in the TGF-β 1/SMAD pathway were significantly upregulated, and Smad7 was down-regulated. Acupotomy treatment reduced the protein and mRNA expression levels of Col-I and Col-III, attenuated the loss of Col-II in cartilage extracellular matrix, and effectively delayed cartilage degeneration in KOA rabbits. This process may be achieved by regulating the factors related to the TGF-β 1/SMAD pathway.Conclusion: In the KOA rabbit model, acupotomy alleviated the degree of fibrosis by regulating factors related to the TGF-β 1/Smad pathway, thereby delaying cartilage degeneration.Keywords: cartilage, fibrosis, TGF-β 1/Smad pathway, acupotomy, knee osteoarthritis