Cbfa1 is a positive regulatory factor in chondrocyte maturation.
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 (Pebp2alphaA/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.
Enomoto
H
H
Department of Molecular Medicine, Osaka University Medical School, 2-2 Yamada-oka Suita, Osaka 565-0871, Japan.
Enomoto-Iwamoto
M
M
Iwamoto
M
M
Nomura
S
S
Himeno
M
M
Kitamura
Y
Y
Kishimoto
T
T
Komori
T
T
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D006984:Hypertrophy; D051379:Mice; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010006:Osteoblasts; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D013977:Tibia / Q000166:cytology; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics
D050659:Core Binding Factor Alpha 1 Subunit; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C493716:Runx2 protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors