Regulation of the chondrocyte phenotype by beta-catenin.
beta-Catenin regulates important biological processes, including embryonic development and tumorigenesis. We have investigated the role of beta-catenin in the regulation of the chondrocyte phenotype. Expression of beta-catenin was high in prechondrogenic mesenchymal cells, but significantly decreased in differentiated chondrocytes both in vivo and in vitro. Accumulation of beta-catenin by the inhibition of glycogen synthase kinase-3beta with LiCl inhibited chondrogenesis by stabilizing cell-cell adhesion. Conversely, the low level of beta-catenin in differentiated articular chondrocytes was increased by post-translational stabilization during phenotypic loss caused by a serial monolayer culture or exposure to retinoic acid or interleukin-1beta. Ectopic expression of beta-catenin or inhibition of beta-catenin degradation with LiCl or proteasome inhibitor caused de-differentiation of chondrocytes. Transcriptional activation of beta-catenin by its nuclear translocation was sufficient to cause phenotypic loss of differentiated chondrocytes. Expression pattern of Jun, a known target gene of beta-catenin, is essentially the same as that of beta-catenin both in vivo and in vitro suggesting that Jun and possibly activator protein 1 is involved in the beta-catenin regulation of the chondrocyte phenotype.
Ryu
Je-Hwang
JH
Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500-712, Korea.
Kim
Song-Ja
SJ
Kim
Seon-Hee
SH
Oh
Chun-Do
CD
Hwang
Sang-Gu
SG
Chun
Churl-Hong
CH
Oh
Seung-Hyun
SH
Seong
Je-Kyung
JK
Huh
Tae-Lin
TL
Chun
Jang-Soo
JS
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo / Q000033:anatomy & histology / Q000502:physiology; D019902:Chondrocytes / Q000187:drug effects / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007375:Interleukin-1 / Q000494:pharmacology; D008648:Mesoderm / Q000166:cytology; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin
D024043:Collagen Type II; D003598:Cytoskeletal Proteins; D007375:Interleukin-1; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D051176:beta Catenin