[Effect of acupotomy on expressions of cellular senescence markers p16Ink4a and p21Waf1/Cip1 in cartilage tissue of rabbits with knee osteoarthritis].

Objective: To observe the effect of acupotomy on the expressions of p16^Ink4a and p21^Waf1/Cip1 in knee osteoarthritis (KOA) rabbits，so as to analyze whether acupotomy can treat KOA by inhibiting the cellular senescence of chondrocytes.

Methods: Twenty-four New Zealand male rabbits were randomly divided into normal, model, acupotomy and electroacupuncture (EA) groups, with 6 rabbits in each group. The KOA model was established by left hindlimb straightening fixation. After modeling, rabbits in the acupotomy group were treated with acupotomy loosening therapy on high stress points around the affected knee joints such as tendons attachment points of vastus medialis, vastus lateralis, rectus femoris, biceps femoris and pes anserine bursa, once a week for 3 weeks. In the EA group, "Xuehai"(SP10), "Liangqiu" (ST34),"Neixiyan" (EX-LE4) and "Waixiyan" (ST35) on the affected hindlimb were selected for EA treatment (3 mA, 2 Hz/100 Hz), 20 min each time, once every other day for 3 weeks. Before and after treatments, the knee Lequesne MG score and passive range of motion (PROM) of the affected knee joint were evaluated. After the treatments, the expressions of p16^Ink4a and p21^Waf1/Cip1 in the cartilage tissue of the affected knee joint were detected by immunohistochemistry and Western blot respectively.

Results: Before and after treatment, compared with the normal group, the Lequesne MG score was significantly increased (P<0.01), the PROM was significantly decreased (P<0.01) in the model group. After treatment, compared with the normal group, the positive expression and protein expression levels of p16^Ink4a and p21^Waf1/Cip1 were significantly increased (P<0.01) in the model group; compared with the model group, the Lequesne MG score was significantly decreased (P<0.01), the PROM was significantly increased (P<0.01), the positive expression and protein expression levels of p16^Ink4a and p21^Waf1/Cip1 were significantly decreased (P<0.01，P<0.05) in the acupo-tomy and EA groups; compared with the EA group, the Lequesne MG score was decreased (P<0.05), the PROM was increased (P<0.05), the positive expression and protein expression levels of p16^Ink4a and p21^Waf1/Cip1 were decreased (P<0.05，P<0.01) in the acupotomy group.

Conclusion: Acupotomy intervention can down-regulate the expressions of cellular senescence markers p16^Ink4a and p21^Waf1/Cip1 in chondrocytes, indicating that acupotomy therapy may alleviate cartilage degeneration by inhibiting chondrocyte premature cellular senescence to treat KOA.