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Signaling of monocytic differentiation by a non‐hypercalcemic analog of vitamin D 3 , 1,25(OH) 2 ‐5,6 trans‐16‐ene‐vitamin D 3 , involves nuclear vitamin D receptor (nVDR) and non‐nVDR–mediated pathways
Author(s) -
Ji Yan,
Wang Xuening,
Donnelly Robert J.,
Uskokovic Milan R.,
Studzinski George P.
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10091
Subject(s) - downregulation and upregulation , calcitriol receptor , cellular differentiation , monocyte , vitamin , vitamin d and neurology , receptor , microbiology and biotechnology , chemistry , cd14 , endocrinology , medicine , biology , biochemistry , immunology , gene
Exposure of leukemia cells to the physiologically active form of vitamin D 3 , 1,25‐dihydroxyvitamin D 3 (1,25D 3 ) normalizes their phenotype to cells that resemble mature monocytes. One of the earliest detectable events in this process is an upregulation of the nuclear receptor for 1,25D 3 , the vitamin D receptor (nVDR). In contrast, the novel analog of 1,25D 3 , 1,25‐dihydroxy‐5,6 trans‐16‐ene‐vitamin D 3 (5,6‐16D 3 ), which has recently been reported to have low calcium‐mobilizing activity in vivo, rapidly induced the expression of CD14, CD11b, and monocyte‐specific esterase (MSE), classical markers of the mature monocyte, but upregulated nVDR expression less than 1,25D 3 . This upregulation was shown to be the result of altered degradation of the nVDR protein, while the levels of nVDR mRNA were constant. Knock‐out of nVDR transcriptional activity by a decoy VDRE double‐stranded deoxyoligonucleotide, markedly abrogated 1,25D 3 ‐induced differentiation, but incompletely inhibited 5,6‐16D 3 ‐induced differentiation. These findings suggest that the unique ability of 5,6‐16D 3 to induce cell differentiation but not systemic hypercalcemia, may be due to the activation of pathways which initiate differentiation independently of nVDR. J. Cell. Physiol. 191: 198–207, 2002. © 2002 Wiley‐Liss, Inc.