Exp Mol Med.  2006 Aug;38(4):401-407.

Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway

• Kim DJ
• Chung JH
• Ryu EK
• Rhim JH
• Ryu YS
• Park SH
• Kim KT
• Kang HS
• Chung HK
• Park SC

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.

Keyword

apoptosis; chondrocytes; ossification; Fas ligand; guanosine

MeSH Terms

Tumor Necrosis Factors/metabolism
Signal Transduction/drug effects
Receptors, Tumor Necrosis Factor/*metabolism
Rats, Sprague-Dawley
Rats
Nucleoside Transport Proteins/metabolism
Membrane Glycoproteins/metabolism
Guanosine/*pharmacology/physiology
Fas Ligand Protein
Chondrocytes/*drug effects/metabolism
Apoptosis/*drug effects
Antigens, CD95
Animals