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首页> 外文期刊>british journal of haematology >Myeloid progenitors from the bone marrow of patients with vitamin D resistant rickets (type II) fail to respond to 1,25(OH)2D3
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Myeloid progenitors from the bone marrow of patients with vitamin D resistant rickets (type II) fail to respond to 1,25(OH)2D3

机译:Myeloid progenitors from the bone marrow of patients with vitamin D resistant rickets (type II) fail to respond to 1,25(OH)2D3

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SummaryThe active metabolite of vitamin D, 1,25‐dihyd‐roxyvitamin D3(1,25(OH)2D3), has been shown to enhance the growth of human granulocyte/macrophage haemopoietic progenitorsin vitroand to induce these cells to differentiate along the monocyte/macrophage pathway. In order to evaluate the relationship between specific receptors for 1,25(OH)2D3and the role of 1,25(OH)2D3in the regulation of haemopoietic cell differentiation, we examined the effect of 1,25(OH)2Di on thein vitrogrowth and differentiation patterns of marrow myeloid progenitor cells from two patients with 1,25(OH)2D3resistant rickets, resulting from defective receptors to vitamin D. A significant rise in the frequency of myeloid colonies in control marrow cell cultures was induced by 2×10−9to 2×10−7M 1,25(OH)2D3. This rise reached a plateau at 2×10−9–2×10−8M 1,25(OH)2D3, resulting in a maximal 54±9 increase in colony numbers. In contrast, no stimulatory effect could be detected when 1,25(OH)2D3was added to cultured marrow cells from the patients with 1,25(OH)2D5resistance. Analysis of colony composition revealed that 2×10−8and 2×10−7M, 1,25(OH)2D3induced a 50±26 increase in the frequency of colonies composed only of monocytes/macrophages in control, but not in the patients’marrow cell cultures. The effect of 2×10−8and 2×10−7M 1,25(OH)2D3on progenitor cell differentiation towards monocytes/macrophages was also observed in marrow cell suspension cultures. Whereas 1,25(OH)2D3induced a 81–136 increase in the frequency of monocytes in control marrow cells, no effect could be detected on the generation of mature monocytes in marrow cells of the 1,25(OH)2D3resistant patients. Our results show that marrow granulocyte/macrophage progenitor cells from patients with 1,25(OH)2D3resistance fail to respond to 1,25(OH)2D3. We thus demonstrate that the effect of 1,25(OH)2D3on the proliferation and differentiation of haemopoietic progenitor cells is mediated through its bindin

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