TY - JOUR T1 - Apoptosis in Microencapsulated Juvenile Rabbit Chondrocytes Induced by Ofloxacin: Role Played by β<sub>1</sub>-Integrin Receptor JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 155 LP - 165 DO - 10.1124/jpet.106.118224 VL - 322 IS - 1 AU - Zhi-guo Sheng AU - Shuangqing Peng AU - Chang-yong Wang AU - Hong-bo Li AU - Ravindra K. Hajela AU - Yim-ei Wang AU - Qian-qian Li AU - Mi-feng Liu AU - Yan-sheng Dong AU - Gang Han Y1 - 2007/07/01 UR - http://jpet.aspetjournals.org/content/322/1/155.abstract N2 - Quinolone(s) (QNs) is widely used in infection therapy due to its good antimicrobial characteristics. However, QNs-induced arthropathy of immature animals has led to restrictions on the therapeutic use of these antimicrobial agents. The exact mechanism(s) of QNs-induced chondrotoxicity remain unknown. In the present study, we investigated the possible mechanism of ofloxacin (one typical QNs)-induced injuries of chondrocytes. Juvenile rabbit joint chondrocytes cultured in alginate microspheres were incubated with ofloxacin at concentrations of 0, 2, 5, 10, 20, and 40 μg/ml for up to 96 h. Concentration of 10 μg/ml ofloxacin induced apoptosis of chondrocyte with visible apoptotic signs, including degradation of poly(ADP-ribose) polymerase, caspase-3 activation, and DNA ladder formation. Furthermore, extracellular signal-regulated kinase 1/2 (phospho-ERK1/2) and growth factor receptor-bound protein 2 (Grb2) were significantly reduced, and similar changes were also observed in the β1-integrin receptor as assessed by immunoblotting. However, the mRNA level of β1-integrin obtained from reverse transcription-polymerase chain reaction remained unchanged. Results of β1-integrin immunoprecipitation have also shown that β1-integrin did not interact with activated intracellular signaling proteins. In addition, ofloxacin did not induce apoptosis and decrease β1-integrin expression in chondrocytes supplemented with Mg2+, and the ofloxacin-induced apoptosis was caspase-8-dependent, inhibition of which did not affect the expression mode of phospho-ERK1/2 and β1-integrin. Our results demonstrate that ofloxacin affects β1-integrin receptor functions and the ERK mitogen-activated protein kinase signaling pathway, causing caspase-8-dependent apoptosis after exposure of 48 h. The American Society for Pharmacology and Experimental Therapeutics ER -