Billecocq A, Emanuel J R, Levenson R, Baron R
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1990 Aug;87(16):6470-4. doi: 10.1073/pnas.87.16.6470.
1 alpha,25-Dihydroxyvitamin 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.
1α,25 - 二羟维生素D3[1,25(OH)2D3]是类固醇激素维生素D的活性代谢产物,是巨噬细胞和破骨细胞分化的有效调节剂。与循环单核细胞或组织巨噬细胞不同,成熟破骨细胞表达高水平的碳酸酐酶II(CAII)。该酶从水和二氧化碳生成质子和碳酸氢盐,并参与骨吸收和酸碱调节。为了测试1,25(OH)2D3是否能诱导骨髓单核细胞前体向破骨细胞而非巨噬细胞分化,我们分析了其对含有两种细胞类型共同前体的骨髓培养物中CAII表达的影响。1,25(OH)2D3以剂量和时间依赖性方式显著增加CAII的表达。在骨髓中,这种增加发生在mRNA和蛋白质水平,并且在刺激后24小时就可检测到。还发现1,25(OH)2D3在转化的骨髓单核细胞禽细胞系中诱导CAII表达。这些结果表明,1,25(OH)2D3调节骨髓单核细胞前体表达CAII的水平,CAII是一种参与成熟破骨细胞功能的酶。