Cbfa1 Is a Positive Regulatory Factor in Chondrocyte Maturation

• Published in: The Journal of biological chemistry 2000-03, Vol.275 (12), p.8695-8702
• Main Authors: Enomoto, Hirayuki, Enomoto-Iwamoto, Motomi, Iwamoto, Masahiro, Nomura, Shintaro, Himeno, Miki, Kitamura, Yukihiko, Kishimoto, Tadamitsu, Komori, Toshihisa
• Format: Article
• Language: English
• Subjects: Animals; Cbfa1 protein; Cell Differentiation - drug effects; Chick Embryo; Chondrocytes - cytology; Chondrocytes - metabolism; Core Binding Factor Alpha 1 Subunit; DNA, Complementary - genetics; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - classification; DNA-Binding Proteins - genetics; Hypertrophy; Mice; MMP13 gene; Neoplasm Proteins; Oligonucleotides, Antisense - pharmacology; Osteoblasts; Phenotype; RNA, Messenger - analysis; Tibia - cytology; Transcription Factor AP-2; Transcription Factors - biosynthesis; Transcription Factors - classification; Transcription Factors - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.12.8695

Cbfa1 is a transcription factor that belongs to the runt domain gene family. Cbfa1-deficient mice showed a complete lack of bone formation due to the maturational arrest of osteoblasts, demonstrating that Cbfa1 is an essential factor for osteoblast differentiation. Further, chondrocyte maturation was severely disturbed in Cbfa1-deficient mice. In this study, we examined the possibility that Cbfa1 is also involved in the regulation of chondrocyte differentiation. mRNAs for both Cbfa1 isotypes, type I Cbfa1 (Pebp2αA/Cbfa1) and type II Cbfa1 (Osf2/Cbfa1 or til-1), which are different in N-terminal domain, were expressed in terminal hypertrophic chondrocytes as well as osteoblasts. In addition, mRNA for type I Cbfa1 was expressed in other hypertrophic chondrocytes and prehypertrophic chondropcytes. In a chondrogenic cell line, ATDC5, the expression of type I Cbfa1 was elevated prior to differentiation to the hypertrophic phenotype, which is characterized by type X collagen expression. Treatment with antisense oligonucleotides for type I Cbfa1 severely reduced type X collagen expression in ATDC5 cells. Retrovirally forced expression of either type I or type II Cbfa1 in chick immature chondrocytes induced type X collagen and MMP13 expression, alkaline phosphatase activity, and extensive cartilage-matrix mineralization. These results indicate that Cbfa1 is an important regulatory factor in chondrocyte maturation.