Abstract: OBJECTIVE To study the effect and mechanism of the extract of Clematis chinensis Osbeck(CCO) on the phenotypic maintenance of rabbit chondrocytes in simulated microgravity culture environment.METHODS Rotary Cell Culture system(RCC) was used to simulate microgravity environment in vitro, and the extract of CCO was used to interfere with chondrocyte. The rabbit knee joint cartilage cells were extracted and divided into 4 groups: blank(two dimensions on plate), CCO(two dimensions on plate, with CCO), microgravity group(cultured in RCC), RCC-CCO(cultured in RCC, with CCO). All were cultured for 7 d. Morphological changes of chondrocytes were observed. Chondrocyte proliferation was detected by CCK8 and apoptotic rate were detected using flow cytometry. The chondrogenic differentiation related mRNA expression of Collagen type Ⅱ, aggrecan, TGF-β, SOX9 and chondrogenic dedifferentiation related mRNA MMP13, collagen type Ⅰ were detected. The protein expression of type Ⅱ collagen, aggrecan, TGF-β and MMP13 were detected by Western blotting. And energy metabolism was assessed by detecting concentration of intracellular glucose, ATP and lactate.RESULTS Chondrocytes in RCC group and RCC-CCO group maintained good morphology, while the spindle cells in control group and CCO group increased. Compared with the Control group, both the microgravity conditions and the CCO could increase the proliferation activity of chondrocytes at 48 h and 72 h, reduce the apoptotic rate of chondrocytes. Then, they could up-regulate the protein and mRNA expression of proteoglycan, type Ⅱ collagen and TGF-β, decrease MMP13 protein and mRNA expression, up-regulate SOX9 mRNA expression, decrease type Ⅰ collagen mRNA expression, and up-regulate glucose, ATP, and lactic acid content in chondrocytes. Combining of the two was more significant (P < 0.01).CONCLUSION The simulated microgravity culture environment and the extract of CCO can promote the energy metabolism of chondrocytes, maintain the proliferative activity and the phenotype of chondrocytes, and the combined application of the two can play a synergistic role.