Cbfa1 Is a Master Gene for Osteoblast Differentiation
A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is expressed restrictively in fetal development. Cbfa1 expression was first detected at embryonic day 9.5, which is four days earlier than the beginning of ossification, and was preferentially detected in the osteoblast lineage during osteogenesis. Cbfa1 deficient mice lacked both intramembranous and endochondral ossification completely. The skeletons of the mutant mice are composed of cartilage and fibrous tissues in calvaria. Cbfa1 mutant mice expressed alkaline phosphatase and osteonectin, which are the markers for osteoprogenitors, but not osteopontin and osteocalcin, which are the markers for immature osteoblasts and mature osteoblasts respectively. Therefore, the differentiation of osteoblast was blocked in the mutant mice. Further, Cbfa1 expression in nonosteoblastic cells induced osteoblastic markers in vitro. These data demonstrate that Cbfa1 is an essential transcription factor for osteoblast differentiation. The maturational disturbance of osteoclast and chondrocyte was also observed in the mutant mice, indicating the direct or indirect role of Cbfa1 in the differentiation of osteoclast and chondrocyte. Heterozygously mutated mice in the Cbfa1 locus showed the similar phenotype with cleidocranial dysplasia, which is an autosomal inherited disease. The mutations of CBFA1 locus were identified in cleidocranial dysplasia patients.
Key wordsCbfa1 Runt-domain gene family Osteoblast differentiation Cleidocranial dysplasia Bone formation
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