title: Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway.
abstract: 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.
authors.affiliation: Metabolic Engineering Laboratory Inc., Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Dong-Jo
authors.initials: DJ
authors.lastname: Kim
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Chung
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Ryu
authors.forename: Jung-Hyo
authors.initials: JH
authors.lastname: Rhim
authors.forename: Yoon-Sic
authors.initials: YS
authors.lastname: Ryu
authors.forename: So-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Kim
authors.forename: Heun-Soo
authors.initials: HS
authors.lastname: Kang
authors.forename: Hong-Keun
authors.initials: HK
authors.lastname: Chung
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
mesh_terms: 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
chemical_list: 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