Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3.

Publisher Website
Google Scholar
Abstract
1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates bone resorption in man and other vertebrates, in part, by increasing the number of osteoclasts, the principal resorbing cells of bone. Because osteoclasts are very likely derived from a member(s) of the mononuclear phagocyte family, whether 1,25(OH)2D3 promotes maturation of these cells was determined by studying its effects on the human promyelocytic leukemia cell line HL-60. Of the vitamin D3 metabolites tested, only 1,25(OH)2D3, at 10-10 to 10-7 M, induces the differentiation of HL60 into mono- and multinucleated macrophage-like cells. Phenotypic change is evident within 24 h and reaches a plateau between 72 and 96 h of incubation. The changes are metabolite-specific and include adherence to substrate; acquisition of the morphological features of mature monocytes; a 4- to 6-fold enhancement in lysozyme synthesis and secretion; increase in the fraction of .alpha.-naphthyl acetate esterase-positive cells from .apprx. 2-100% of the population; and the acquisition of several monocyte-associated cell surface antigens. Treated HL-60 cells acquire the capacity to bind and degrade bone matrix, 2 of the essential, functional characteristics of osteoclasts and related bone-resorbing cells. These results, considered together with the reported action of 1,25(OH)2D3 on nontransformed mononuclear cells, are consistent with the view that vitamin D3 enhances bone resorption and osteoclastogenesis in vivo by promoting the differentiation of precursor cells.