Divergent regulation of 1,25-dihydroxyvitamin D-3 on human bone marrow osteoclastogenesis and myelopoiesis

The physiologically active form of vitam in D-3, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) has influence over osteoclastogenesis and myelopoiesis, bu t the regulational mechanism is not well-defined. In this report, formation of osteoclast-like (OCL) cells from primitive myeloid colony-forming cells (PM-CFC) as mediated by 1,25(OH)(2)D-3 was examined. Our results present i n this report clearly show that 1,25(OH)(2)D-3 dose-dependently stimulated OCL cell formation when added to suspension cultures of individually replat ed PM-CFC colonies. Marrow cells were plated with either granulocyte-macrop hage colony-stimulating factor (GM-CSF) or the human bladder carcinoma cell line 5637 conditioned medium (5637 CM) as the source of colony-stimulating activity. The 1,25(OH)(2)D-3 effect of osteoclast differentiation was asso ciated with a concomitant decrease in clonogenic growth of myelopoietic pro genitors in response to colony-stimulating activity. Secondly, the effect o f adding the known stimulator of hematopoiesis, interleukin-1 beta (IL-1 be ta) and/or 1,25(OH)(2)D-3 on human myeloid colony growth was assessed. IL-1 beta enhanced the formation of primitive myeloid colonies in response to G M-CSF by 160%. On the other hand, 1,25(OH)2D3 dose-dependently inhibited bo th GM-CSF- and 5637 CM-driven myeloid colony formation by as much as 90% at 100 nM. Addition of IL-1 beta to GM-CSF-stimulated cultures dampened the i nhibitory effect of 1,25(OH),D3. The inhibition of myeloid clonogenic growt h by 1,25(OH)(2)D-3 was almost abolished (89%) by simultaneously adding ant i-tumor necrosis tactor-alpha monoclonal antibody (anti-TNF-alpha MoAb) to the culture medium. These results collectively suggest divergent roles for 1,25(OH)(2)D-3 in osteoclastogenesis and myelopoiesis, promoting the differ entiation of OCL cells from primitive myeloid cells but inhibiting the prol iferation of later myeloid progenitor cells. This inhibition of myeloid pro genitors may be mediated by TNF-alpha.J. Cell. Biochem. 72:387-395, 1999. ( C) 1999 Wiley-Liss, Inc.