Yunxuan Ma,1,* Tingyao Hu,1,* Naigang Liu,2 Changqing Guo,1 Longfei Xing,3 Weiwei Ma,4 Yongqi Cui,1 Xilin Chen5 

1School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Acupuncture-moxibustion, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Traditional Chinese Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 4Department of Traditional Chinese Medicine, Wuzhong People ‘s Hospital, Ningxia, People’s Republic of China; 5Department of Acupuncture and Rehabilitation, The Fifth College of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Naigang Liu, Department of Acupuncture, China-Japan Friendship Hospital, Beijing, 100010, People’s Republic of China, Tel +86-13488782471, Fax +86-1084205333, Email liunaigang1983@163.com

Purpose: Premature senescence of chondrocytes is a typical lesion of knee osteoarthritis (KOA). Abnormal cartilage stress can inhibit the mechanosensitive Yes-associated protein (YAP) / transcription factor forkhead box D1 (FOXD1) pathway, which is related to premature senescence of chondrocytes, thereby accelerating the progression of the lesion. This study aims to investigate whether acupotomy intervention could inhibit the premature senescence of chondrocytes and protect the cartilage of KOA rabbits.
Methods: 18 male New Zealand rabbits were randomly divided into 3 groups (n = 6 each): control, KOA, and KOA + acupotomy (KOA+Apo). KOA, KOA+Apo rabbits were modeled by modified Videman’s method for 6 weeks. After modeling, the KOA+Apo groups were subjected to acupotomy once a week for 3 weeks on the muscles around the left hind knee. The modified Lequesne MG score and passive range of motion (PROM) were used to evaluate the general condition and exercise ability of rabbits. Cartilage degeneration was detected by safranin O-fast green staining and transmission electron microscope(TEM). Type II collagen (Col-II) and aggrecan by immunohistochemistry (IHC), IL-7 and MMP-13 by Enzyme-Linked Immunosorbent Assay (ELISA), and p53, Rb1, p - YAP, YAP, FOXD1 by IHC, Western blot, or RT - PCR.
Results: Acupotomy effectively curbed cartilage degeneration and chondrocyte premature senescence in KOA rabbits. Mechanistically, it cut IL - 7 and MMP-13 levels, easing the inflammatory milieu and extracellular matrix degradation. It also regulated p53 and Rb1, controlling cell - cycle progression. Crucially, acupotomy upregulated the YAP/FOXD1 pathway, which, by affecting downstream genes, modulated IL - 7, MMP-13, p53, and Rb1 levels, acting as a pivotal molecular link in its regulatory effects.
Conclusion: Acupotomy may protect KOA rabbits’ cartilage by inhibiting chondrocytes premature senescence via the YAP/FOXD1 pathway, offering a new theoretical basis for treating mechanically - induced KOA.

Keywords: acupotomy, knee osteoarthritis, chondrocytes, premature senescence, YAP/FOXD1 pathway