Esophageal cancer related gene 4 (ECRG4) is a marker of articular chondrocyte differentiation and cartilage destruction.
With the aim of identifying novel genes regulating cartilage development and degeneration, we screened a cartilage-specific expressed sequence tag database. Esophageal cancer related gene 4 (ECRG4) was selected, based on the criteria of 'chondrocyte-specific' and 'unknown function.' ECRG4 expression was particularly abundant in chondrocytes and cartilage, compared to various other mouse tissues. ECRG4 is a secreted protein that undergoes cleavage after secretion. The protein is specifically expressed in chondrocytes in a manner dependent on differentiation status. The expression is very low in mesenchymal cells, and dramatically increased during chondrogenic differentiation. The ECRG4 level in differentiated chondrocytes is decreased during hypertrophic maturation, both in vitro and in vivo, and additionally in dedifferentiating chondrocytes induced by interleukin-1beta or serial subculture, chondrocytes of human osteoarthritic cartilage and experimental mouse osteoarthritic cartilage. However, ectopic expression or exogenous ECRG4 treatment in a primary culture cell system does not affect chondrogenesis of mesenchymal cells, hypertrophic maturation of chondrocytes or dedifferentiation of differentiated chondrocytes. Additionally, cartilage development and organization of extracellular matrix are not affected in transgenic mice overexpressing ECRG4 in cartilage tissue. However, ectopic expression of ECRG4 reduced proliferation of primary culture chondrocytes. While the underlying mechanisms of ECRG4 expression and specific roles remain to be elucidated in more detail, our results support its function as a marker of differentiated articular chondrocytes and cartilage destruction.
Huh
Yun Hyun
YH
Cell Dynamics Research Center and BioImaging Research Center, Department of Life Sciences, Gwangju Institute of Science and Technology, Buk-Gu, Gwangju 500-712, Korea.
Ryu
Je-Hwang
JH
Shin
Sun
S
Lee
Dong-Uk
DU
Yang
Siyoung
S
Oh
Kyung-Shin
KS
Chun
Churl-Hong
CH
Choi
Jeong-Keun
JK
Song
Woo Keun
WK
Chun
Jang-Soo
JS
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001846:Bone Development; D002356:Cartilage / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis; D018507:Gene Expression Regulation, Developmental; D018878:Limb Buds / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity
D015415:Biomarkers; D009363:Neoplasm Proteins; C544440:esophageal cancer related gene 4 protein, mouse