title: Wnt-7a causes loss of differentiated phenotype and inhibits apoptosis of articular chondrocytes via different mechanisms.
abstract: Although regulation of chondrogenesis and cartilage development by Wnt signaling is well established, the function of Wnt in the maintenance and destruction of cartilage remains largely unknown. Here we investigated the involvement and regulatory mechanisms of Wnt signaling in cartilage destruction. We found that interleukin-1beta, the primary pro-inflammatory cytokine involved in cartilage destruction, induces expression of Wnt-5a and -7a in primary culture articular chondrocytes. The level of beta-catenin was also increased in chondrocytes of arthritic cartilage, suggesting the association of Wnt/beta-catenin signaling with arthritic cartilage destruction. In addition, our results show that Wnt-7a induces dedifferentiation and inhibits NO-induced apoptosis of primary culture articular chondrocytes. Wnt-7a induces dedifferentiation of articular chondrocytes by stimulating transcriptional activity of beta-catenin, whereas NO-induced apoptosis is inhibited via the activation of cell survival signaling, such as phosphatidylinositol 3-kinase and Akt, which block apoptotic signaling cascade. Our results collectively suggest that Wnt-7a is associated with cartilage destruction by regulating the maintenance of differentiation status and the apoptosis of articular chondrocytes via different mechanisms.
authors.affiliation: Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Je-Hwang
authors.initials: JH
authors.lastname: Ryu
authors.forename: Il-Chul
authors.initials: IC
authors.lastname: Kim
authors.forename: Eek-Hoon
authors.initials: EH
authors.lastname: Jho
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Jung
authors.forename: Kwonseop
authors.initials: K
authors.lastname: Kim
authors.forename: Song-Ja
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jang-Soo
authors.initials: JS
authors.lastname: Chun
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000166:cytology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D007375:Interleukin-1; D015534:Trans-Activators; D051176:beta Catenin; D009569:Nitric Oxide; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases