Identification and characterization of arginase II as a chondrocyte phenotype-specific gene.
We have previously shown that activation of extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) causes chondrocyte dedifferentiation, which contributes to the destruction of arthritic cartilage. In the present study, we identified genes involved in the ERK1/2 regulation of chondrocyte dedifferentiation. Several genes were identified by subtractive hybridization, and, of these, arginase II was selected for further functional characterization. Similar to the pattern of type II collagen expression, which is a hallmark of chondrocyte differentiation, arginase II expression was increased during chondrogenesis of mesenchymal cells. The high expression level of arginase II was decreased during dedifferentiation of chondrocytes, whereas its expression was restored during redifferentiation of the dedifferentiated chondrocytes. Inhibition of ERK1/2 signaling in chondrocytes enhanced type II collagen expression with a concomitant increase in expression and activity of arginase II. However, ectopic expression of arginase II or inhibition of its activity did not affect chondrocyte differentiation. The results collectively indicate that expression of arginase II is specific to the chondrocyte phenotype, although the expression of arginase II alone is not sufficient for articular chondrocytes to maintain a differentiated phenotype.
Ko
Ah-Ra
AR
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea.
Huh
Yun-Hyun
YH
Lee
Hyun-Chae
HC
Song
Woo-Keun
WK
Lee
Young-Sup
YS
Chun
Jang-Soo
JS
D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002358:Cartilage, Articular / Q000166:cytology; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D024043:Collagen Type II / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008969:Molecular Sequence Data; D010641:Phenotype; D011817:Rabbits; D016415:Sequence Alignment; D014018:Tissue Distribution
D024043:Collagen Type II; D004791:Enzyme Inhibitors; D005419:Flavonoids; D053583:Interleukin-1beta; D007527:Isoenzymes; D048049:Extracellular Signal-Regulated MAP Kinases; D001119:Arginase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one