1α,25-Dihydroxyvitamin D₃ regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells

1α,25-Dihydroxy vitamin D₃ [1,25(OH)₂D₃], the active metabolite of the steroid hormone vitamin D, is a potent regulator of macrophage and osteoclast differentiation. The mature osteoclast, unlike the circulating monocyte or the tissue macrophage, expresses high levels of carbonic anhydrase II (CAII). This enzyme generates protons and bicarbonate from water and carbon dioxide and is involved in bone resorption and acid-base regulation. To test whether 1,25(OH)₂D₃ could induce the differentiation of myelomonocytic precursors toward osteoclasts rather than macrophages, we analyzed its effects on the expression of CAII in bone marrow cultures containing precursors common to both cell types. The expression of CAII was markedly increased by 1,25(OH)₂D₃ in a dose-and time-dependent manner. In bone marrow, this increase occurred at the mRNA and protein levels and was detectable as early as 24 hr after stimulation. 1,25(OH)₂D₃ was also found to induce CAII expression in a transformed myelomonocytic avian cell line. These results suggest that 1,25(OH)₂D₃ regulates the level at which myelomonocytic precursors express CAII, an enzyme that is involved in the function of the mature osteoclast.