The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner |
| |
Authors: | Yano Fumiko Kugimiya Fumitaka Ohba Shinsuke Ikeda Toshiyuki Chikuda Hirotaka Ogasawara Toru Ogata Naoshi Takato Tsuyoshi Nakamura Kozo Kawaguchi Hiroshi Chung Ung-Il |
| |
Affiliation: | Division of Tissue Engineering, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan. |
| |
Abstract: | 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. |
| |
Keywords: | Wnt Cartilage Chondrogenic differentiation Hypertrophy LEF-1 β-Catenin Sox9 |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|