Regulatory Mechanism of Osteoblast Differentiation and Bone Formation

抄録

Osteoblast differentiation is regulated by various hormones and local factors such as estrogen, parathyroid hormone , bone morphogenetic proteins ( BMPs ) and hedgehogs . Estrogendeficiency increases systemic factors that stimulate osteoblast differentiation, resulting in a high turnover bone remodeling with accelerated bone formation. Parathyroid hormone has diverse effects on osteoblast differentiation depending on the exposure time in vitro mediated through different signal transduction systems. Among local factors, BMPs are the most potent inducers and stimulators of osteoblast differentiation: BMPs not only stimulate osteoprogenitors to differentiate into mature osteoblasts but also induce non-osteogenic cells to differentiate into osteoblast lineage cells. Sonic and Indian hedgehogs also play important roles in regulation of osteoblast differentiation by interacting with BMPs. Cbfa1, a transcription factor belonging to the runt-domain gene family, is essential for osteoblast differentiation and bone formation because Cbfa1-deficient mice completely lack bone formation due to maturational arrest of osteoblasts. BMPs are important local factors that up-regulate Cbfa1 expression. The phenotype of heterozygous Cbfa1 mutation is similar to that of cleidocranial dysplasia. The intimate interaction between the local factors including hedgehogs and BMPs as well as the transcription factor Cbfa1 play crucial roles in the process of osteoblast differentiation and bone formation. Further progress in bone research will provide information important not only in the field of cell biology but also for clinical research of various bone diseases.