1 alpha,25-dihydroxyvitamin D3 regulates the transcription of carbonic anhydrase II mRNA in avian myelomonocytes.

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RESUMO

Carbonic anhydrase II (CAII) is highly expressed in the osteoclast, where it is involved in the process of extracellular acidification required for bone resorption. We have previously shown that 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], a steroid hormone that regulates the differentiation of macrophages and osteoclasts, induces the expression of CAII mRNA and protein in avian bone marrow cells. To determine whether this regulation occurred at the gene level, we have studied the effects of 1,25(OH)2D3 on CAII expression in a transformed myelomonocytic avian cell line (BM2). As observed in nontransformed cells, 1,25(OH)2D3 markedly increased CAII biosynthesis and mRNA levels. The increase in CAII mRNA was detected as early as 3 hr after adding the hormone (1.9-fold) and reached 4.7-fold by 48 hr. These effects were completely blocked by actinomycin D, and nuclear run-on analysis confirmed that 1,25(OH)2D3 increased the rate of CAII gene transcription. In contrast, induction of CAII mRNA expression was not affected by inhibition of protein synthesis with cycloheximide, and no significant changes in mRNA stability were seen. Thus, 1,25(OH)2D3 modulates CAII gene expression at the transcriptional level, and this effect does not require de novo synthesis of other gene products. These results suggest that activation of the CAII gene occurs early in the differentiation events triggered by vitamin D3 in myelomonocytic cells.

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