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Puerarin can protect chondrocytes, whereby ameliorating osteoarthritis. Puerarin also promotes autophagy. Autophagy maintains chondrocyte homeostasis. The role of autophagy in puerarin-protected chondrocytes is unknown. Puerarin promoted chondrocyte autophagy. Puerarin-protected chondrocytes were reversed by autophagy inhibitors and Beclin1 inhibitor. 3-MA or Beclin1 inhibitor in vivo reversed puerarin-ameliorated cartilage damage of osteoarthritis mice. Thus, puerarin can protect chondrocytes through Beclin1-dependent autophagy activation.