Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway.
Although the apoptosis of chondrocytes plays an important role in endochondral ossification, its mechanism has not been elucidated. In this study, we show that guanosine induces chondrocyte apoptosis based on the results of acridine orange/ethidium bromide staining, caspase-3 activation, and sub-G1 fraction analysis. The potent inhibitory effect of dipyridamole, a nucleoside transporter blocker, indicates that extracellular guanosine must enter the chondrocytes to induce apoptosis. We found that guanosine promotes Fas-Fas ligand interaction which, in turn, leads to chondrocyte apoptosis. These findings indicate a novel mechanism for endochondral ossification via metabolic regulation.
Kim
Dong-Jo
DJ
Metabolic Engineering Laboratory Inc., Seoul National University College of Medicine, Seoul 110-799, Korea.
Chung
Jun-Ho
JH
Ryu
Eun-Kyeong
EK
Rhim
Jung-Hyo
JH
Ryu
Yoon-Sic
YS
Park
So-Hyun
SH
Kim
Kyung Tae
KT
Kang
Heun-Soo
HS
Chung
Hong-Keun
HK
Park
Sang Chul
SC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D053222:Fas Ligand Protein; D006151:Guanosine / Q000494:pharmacology* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D033703:Nucleoside Transport Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D048069:Tumor Necrosis Factors / Q000378:metabolism; D019014:fas Receptor
D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D033703:Nucleoside Transport Proteins; D018124:Receptors, Tumor Necrosis Factor; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D006151:Guanosine