The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner.
To better understand the role of the canonical Wnt signaling pathway in cartilage development, we adenovirally expressed a constitutively active (ca) or a dominant negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear effector of the pathway, in undifferentiated mesenchymal cells, chondrogenic cells, and primary chondrocytes, and examined the expression of markers for chondrogenic differentiation and hypertrophy. caLEF-1 and LiCl, an activator of the canonical pathway, promoted both chondrogenic differentiation and hypertrophy, whereas dnLEF-1 and the gene silencing of beta-catenin suppressed LiCl-promoted effects. To investigate whether these effects were dependent on Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic differentiation and hypertrophy in wild-type, but not in Sox9-deficient, cells. The response of Sox9-deficient cells was restored by the adenoviral expression of Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner.
Division of Tissue Engineering, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan.
Fumiko
F
Yano
Fumitaka
F
Kugimiya
Shinsuke
S
Ohba
Toshiyuki
T
Ikeda
Hirotaka
H
Chikuda
Toru
T
Ogasawara
Naoshi
N
Ogata
Tsuyoshi
T
Takato
Kozo
K
Nakamura
Hiroshi
H
Kawaguchi
Ung-Il
UI
Chung
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D020219:Chondrogenesis / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D055758:SOX9 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins
D006609:High Mobility Group Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins