2022, Vol. 26 ›› Issue (23): 3644-3649

Screening of drugs for inhibiting growth plate chondrocyte apoptosis and the effect of resveratrol on delaying epiphyseal closure in rats

Xie Yan, Li Wuyin, Xing Weipeng, Pei Yuanyuan, Wang Na   

Abstract: BACKGROUND: Epiphyseal closure indicates the long bones stop growing, which is caused by the apoptosis of growth plate chondrocytes. It has been reported that aromatase inhibitors can inhibit the production of estrogen, and the cessation of bone growth is caused by epiphyseal closure. Therefore, it has been inferred that aromatase inhibitors can inhibit growth plate chondrocyte apoptosis and delay epiphyseal closure.  
OBJECTIVE: To compare the effects of several aromatase inhibitors (resveratrol, biochanin A, and flax lignans) on inhibiting the apoptosis of rat growth plate chondrocyte and to verify the effect of resveratrol on delaying epiphyseal closure and promoting the growth of long bones in rats.
METHODS:   Rat tibial and femoral growth plate cartilage samples were dissected, and growth plate chondrocytes were isolated and cultured in vitro by two-step enzyme digestion. Chondrocytes were morphologically observed and identified by inverted phase contrast microscope and type II collagen immunofluorescence experiments. Then interleukin 1β was used to induce apoptosis of growth plate chondrocytes. Cells were cultured with culture medium containing 10, 20, 40, and 60 μmol/L resveratrol, with culture medium containing 5, 10, 20, 30 μmol/L biochanin, or with culture medium containing 1, 10, 20, 40 μmol/L flax lignans to compare the effects of different concentrations of drugs on the apoptosis of growth plate chondrocytes. Resveratrol which had the best effect was administered to rats by gavage to investigate its effect on the epiphyseal closure of rat tibial plateau and the growth of long bones.  
RESULTS AND CONCLUSION: Appropriate concentrations of resveratrol, biochanin A, and flax lignans could inhibit the apoptosis of growth plate chondrocytes to varying degrees. The best drug concentrations for inhibiting cell apoptosis were 40, 10, and 20 μmol/L in sequence, and 40 μmol/L resveratrol had the best effect on inhibiting the apoptosis of growth plate chondrocytes. Administration of 40 mg/kg resveratrol by gavage could delay epiphyseal closure of tibial plateau and promote the growth of long bones in rats. Therefore, resveratrol can promote bone growth during developmental period by prolonging the time of bone growth.
Key words: aromatase inhibitors, growth plate chondrocytes, apoptosis, drug concentration, epiphyseal closure