Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway.
- Author:
Dong Jo KIM
1
;
Jun Ho CHUNG
;
Eun Kyeong RYU
;
Jung Hyo RHIM
;
Yoon Sic RYU
;
So Hyun PARK
;
Kyung Tae KIM
;
Heun Soo KANG
;
Hong Keun CHUNG
;
Sang Chul PARK
Author Information
1. Metabolic Engineering Laboratory Inc., Seoul National University College of Medicine, Seoul 110-799, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
chondrocytes;
ossification;
Fas ligand;
guanosine
- MeSH:
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
- From:Experimental & Molecular Medicine
2006;38(4):401-407
- CountryRepublic of Korea
- Language:English
-
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.
