1 alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to be a hormonally active form of vitamin D3 in the regulation of intracellular and extracellular calcium levels and of differentiation of myeloid cells and epidermal keratinocytes. We found that 1 alpha,24(R)-dihydroxyvitamin D3 (1,24(OH)2D3), a novel synthetic derivative of vitamin D3, is also active in regulating the differentiation of epidermal keratinocytes. 1,24(OH)2D3 had the same affinity as 1,25(OH)2D3 for a receptor isolated from the epidermis of newborn mice. The incubation of mouse epidermal keratinocytes with 1,24(OH)2D3 induced their differentiation in a time- and dose-dependent manner, as determined by the formation of a cornified envelope and an increase in the activity of transglutaminase. 1,24(OH)2D3 inhibited DNA synthesis of epidermal keratinocytes and also increased their cytosolic calcium level. These effects of 1,24(OH)2D3 were similar to, or rather more than, those of physiologically active 1,25(OH)2D3. However, 1,24(OH)2D3 was found to cause less hypercalcemia than 1,25(OH)2D3 when administrated intravenously to rats, suggesting its possible therapeutic value in psoriasis.
Bone remodelling depends on a balance formation and resorption. Little is known of the biological factors involved in bone formation, whereas there is much evidence that physiological factors, such as parathyroid hormone (PTH) and active metabolites of vitamin D3, influence resorption. Cells responsible for osteogenesis and and osteoclasis occur in close proximity, suggesting that both might be controlled by the same physiological factors in the micro-environment of the body fluid. To clarify the factors stimulating bone formation or accelerating osteogenic cell activity, we have examined the effects of vitamin D3 metabolites and PTH on bone formation in vitro. We report here that combinations of those metabolites especially 1 alpha,25-(OH)2D3 and 24R,25-(OH)2D3, directly stimulate calcification on bone synergistically with PTH.
Key Words 1ƒ¿,24(R)25-(OH)3D3, vitamin D metabolites, radioreceptor ASSAY FOR 1ƒ¿, 24(R)25-(OH)3D3 75 response of intestinal calcium transport to 25-hydroxy and 1,25-dihydroxyvitamin D in nephrectomized rats. Endocrinology,
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