Positive and negative regulation of chondrogenesis by splice variants of PEBP2αA/CBFα1 in clonal mouse EC cells, ATDC5
✍ Scribed by Haruhiko Akiyama; Tomohiko Kanno; Hiromu Ito; Anne Terry; Jim Neil; Yoshiaki Ito; Takashi Nakamura
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 600 KB
- Volume
- 181
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
The ␣A type of the ␣ subunit of the polyomavirus enhancer binding protein 2 (PEBP2␣A), also called the core binding factor ␣1 (CBF␣1) or til-1, plays crucial roles in osteogenesis. Little is known, however, about the function of PEBP2␣A in chondrogenesis. Here, we examined the role of PEBP2␣A in chondrogenesis of clonal mouse embryonal carcinoma cells, ATDC5, which are committed as chondroprogenitors. We found that as ATDC5 cells condensed and formed cartilaginous nodules, PEBP2␣A increased, and the level was maintained throughout the process of chondrocytic maturation. When an established dominant negative form of PEBP2␣A was introduced in undifferentiated ATDC5 cells, the cellular condensation and the subsequent processes were inhibited. This inhibition was overcome with BMP-4 treatment, which increased the endogenous expression of PEBP2␣A. Thus, the process of chondrogenesis is regulated by the level of PEBP2␣A activity. Along with the wild-type PEBP2␣A, a splice variant form, til-1 G2, is naturally expressed in ATDC5 cells. In luciferase reporter assays, til-1 G2 not only exhibited a limited ability to transactivate the osteocalcin promoter but also inhibited the activity achieved by the wild-type PEBP2␣A. When til-1 G2 was overexpressed by stable transfection in undifferentiated ATDC5 cells, it inhibited the progression of chondrogenesis. Therefore, we conclude that PEBP2␣A acts as a positive regulator of chondrogenesis, and that this positive effect may be finely tuned by the opposing effect of the til-1 G2 isoform.