Role of basic helix-loop-helix SCL protein in osteoclast differentiation

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The present study was conducted to determine whether SCL (stem-cell leukemia) protein, a member of basic helix-loop-helix (bHLH) class of transcriptional factors, implicates in osteoclast formation or function of mature osteoclasts.Antisense s-oligonucleotide (2muM) includeing the translation initiation region of the mouse SCL gene inhibites pit formation in a dose-dependent manner, but not inhibites TRAP-positive cell formation. The SCL gene expression was observed by using the RT-PCR technique. Although the constitutive SCL gene expression decreases in time-dependent manner when 14-day-old mouse embryonic calvarial cells are cultured in the absence of 1alpha, 25- (OH)_2D_3, in the presence of 1alpha, 25- (OH)_2D_3, the SCL gene expression decreases transiently on day 3 after the initiation of the culture, and then the gene expression increases on day 5 again. In addition, the SCL gene expression is also observed in mature osteoclast-enriched population. In constrast with these observation, the constitutive expression of SCL gene in early myeloid cell line M1 cells was disappeared in 1alpha, 25- (OH)_<>D_3 treatment-time dependent manner. Antisense SCL s-oligonucleotide inhibits pit formation evenwhen the antisense oligomer is added to TRAP-positive cell forming the late stage cells. In addition, the inhibition of pit formation by antisense SCL s-oligonucleotide is observed in bone cells including mature osteoclasts prepared from 6-day-old mice femora. These results suggest that SCL protein is involved in the exhibition of bone-resorbing function of osteolasts.