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Characteristics of NaF‐induced differentiation of HL‐60 cells
Author(s) -
Kawase Tomoyuki,
Oguro Akira,
Orikasa Michiaki,
Burns Douglas M.
Publication year - 1996
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650111111
Subject(s) - sodium fluoride , chemistry , endocrinology , bone resorption , medicine , nitric oxide , cellular differentiation , nitric oxide synthase , microbiology and biotechnology , fluoride , biochemistry , biology , inorganic chemistry , gene
Sodium fluoride (NaF) is known to stimulate osteoblastic bone formation, but little attention has been given to the possibility that NaF also affects bone resorption and the differentiation of osteoclastic progenitor cells. When human promyelocytic HL‐60 cells were treated with NaF (0.5 mM, 0–4 days), cell proliferation was inhibited, and the addition of 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) (10 nM, 0–4 days) augmented this antiproliferative effect. NaF increased cellular reduction of nitroblue tetrazolium (NBT), and this effect was strongly augmented by 1,25(OH) 2 D 3 . In addition, NaF produced marked changes in cellular morphology, increased cellular adhesion to plastic, reduced the nuclear/cytoplasmic ratio, and increased cellular expression of chloroacetate esterase, but failed to alter cellular nonspecific esterase activity. Furthermore, NaF increased expression of CD11b and CD66b, and this stimulation was enhanced by adding 1,25(OH) 2 D 3 . The sum of these changes in classical promyelocytic cellular indices suggest: (1) that NaF stimulates the early stages of HL‐60 differentiation toward a granulocyte‐like cell and (2) that 1,25(OH) 2 D 3 promotes these actions of NaF. Additional experiments aimed at further understanding the NaF‐induced conversion of HL‐60 cells identified further changes. NaF also increased cellular production of prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) and induced expression of inducible nitric oxide synthase (iNOS); 1,25(OH) 2 D 3 once again augmented these NaF‐induced effects. Similarly, NaF stimulated the production of interleukin 1α (IL‐1α), IL‐6, and tumor necrosis factor‐α, and 1,25(OH) 2 D 3 again strongly enhanced these effects. Indomethacin completely blocked stimulation of NBT reduction, NO production, and iNOS expression induced by NaF plus 1,25(OH) 2 D 3 ; adding exogenous PGE 2 (0.1‐10 ng/ml) to these indomethacin‐blocked cultures dose‐dependently restored NO production. These additional findings together with the observed slow onset (24‐48 h) of NaF and 1,25(OH) 2 D 3 interaction strongly suggest that 1,25(OH) 2 D 3 acts as a cofactor with NaF primarily through interaction with an endogenous NaF‐induced cyclo‐oxygenase product(s), quite possibly PGE 2 itself. Such a mechanism for NaF and 1,25(OH) 2 D 3 interaction would be strongly analogous to the interaction we have recently demonstrated between 1,25(OH) 2 D 3 and PGE 1 on the differentiation of HL‐60 cells. (J Bone Miner Res 1996;11:1676‐1687)