title: Regulation of the chondrocyte phenotype by beta-catenin.
abstract: 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.
authors.affiliation: Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Je-Hwang
authors.initials: JH
authors.lastname: Ryu
authors.forename: Song-Ja
authors.initials: SJ
authors.lastname: Kim
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Chun-Do
authors.initials: CD
authors.lastname: Oh
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Je-Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Tae-Lin
authors.initials: TL
authors.lastname: Huh
authors.forename: Jang-Soo
authors.initials: JS
authors.lastname: Chun
mesh_terms: 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
chemical_list: D024043:Collagen Type II; D003598:Cytoskeletal Proteins; D007375:Interleukin-1; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D051176:beta Catenin