1α,25-Dihydroxyvitamin D3[1α,25-(OH)2D3]-26,23-lactone inhibits 1,25-(OH)2D3-mediated fusion of mouse bone marrow mononuclear cells

S. Ishizuka, Noriyoshi Kurihara, S. Hakeda, N. Maeda, K. Ikeda, M. Kumegawa, A. W. Norman

Research output: Contribution to journalArticle

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Abstract

Vitamin D3 and its hormonally active metabolite 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] can be metabolized to a number of daughter metabolites, including 1α,25-(OH)2D3-26,23-lactone; this latter compound has four diastereoisomers. The 23(S),25(R)-lactone (naturally occurring) and the 23(R),25(S)-1α,25-(OH)2D3-26,23-lactone are both known to be able to inhibit bone resorption induced by 1α,25-(OH)2D3 under in vivo or in vitro conditions. To understand the mechanism of the inhibitory action of these two isomers on bone resorption we investigated the effects of 1α,25-(OH)23-26,23-lactone on unfractionated mouse bone marrow cells in vitro. The addition of 1α,25-(OH)2D3 to these cultures dose-dependently stimulated the formation of multinucleated cells over a range of 10-9-10-7 M. The 23(S),25(S)- and 23(R),25(R)-1α,25-(OH)2D3-26,23-lactones also increased the number of multinucleated cells, whereas the 23(S),25(R)- and 23(R),25(S)-1α,25-(OH)2D3-26,23-lactones failed to do so. In addition, these latter two diastereomers inhibited the 1α,25-(OH)2D3 stimulation of multinucleated cell formation, although the 23(S),25(S)- and 23(R),25(R)-1α,25-(OH)2D3-26,23-lactones and 24R,25-(OH)2D3 did not. These multinucleated cells responded to calcitonin and contained tartrate-resistant acid phosphatase, both of which are characteristic of osteoclasts. The present data suggest that inhibition of multinucleated cell formation is the mechanism by which the 23(S),25(R)- or 23(R),25(S)-1α,25-(OH)2D3-26,23-lactone inhibits bone resorption induced by 1α,25-(OH)2D3.

Original languageEnglish (US)
Pages (from-to)781-786
Number of pages6
JournalEndocrinology
Volume123
Issue number2
StatePublished - 1988
Externally publishedYes

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Calcitriol
Bone Marrow Cells
Lactones
Bone Resorption
Cholecalciferol
Calcitonin
Osteoclasts
Cell Count
1,25-dihydroxyvitamin D3-26,23-lactone
In Vitro Techniques

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Ishizuka, S., Kurihara, N., Hakeda, S., Maeda, N., Ikeda, K., Kumegawa, M., & Norman, A. W. (1988). 1α,25-Dihydroxyvitamin D3[1α,25-(OH)2D3]-26,23-lactone inhibits 1,25-(OH)2D3-mediated fusion of mouse bone marrow mononuclear cells. Endocrinology, 123(2), 781-786.

1α,25-Dihydroxyvitamin D3[1α,25-(OH)2D3]-26,23-lactone inhibits 1,25-(OH)2D3-mediated fusion of mouse bone marrow mononuclear cells. / Ishizuka, S.; Kurihara, Noriyoshi; Hakeda, S.; Maeda, N.; Ikeda, K.; Kumegawa, M.; Norman, A. W.

In: Endocrinology, Vol. 123, No. 2, 1988, p. 781-786.

Research output: Contribution to journalArticle

Ishizuka, S, Kurihara, N, Hakeda, S, Maeda, N, Ikeda, K, Kumegawa, M & Norman, AW 1988, '1α,25-Dihydroxyvitamin D3[1α,25-(OH)2D3]-26,23-lactone inhibits 1,25-(OH)2D3-mediated fusion of mouse bone marrow mononuclear cells', Endocrinology, vol. 123, no. 2, pp. 781-786.
Ishizuka, S. ; Kurihara, Noriyoshi ; Hakeda, S. ; Maeda, N. ; Ikeda, K. ; Kumegawa, M. ; Norman, A. W. / 1α,25-Dihydroxyvitamin D3[1α,25-(OH)2D3]-26,23-lactone inhibits 1,25-(OH)2D3-mediated fusion of mouse bone marrow mononuclear cells. In: Endocrinology. 1988 ; Vol. 123, No. 2. pp. 781-786.
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abstract = "Vitamin D3 and its hormonally active metabolite 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] can be metabolized to a number of daughter metabolites, including 1α,25-(OH)2D3-26,23-lactone; this latter compound has four diastereoisomers. The 23(S),25(R)-lactone (naturally occurring) and the 23(R),25(S)-1α,25-(OH)2D3-26,23-lactone are both known to be able to inhibit bone resorption induced by 1α,25-(OH)2D3 under in vivo or in vitro conditions. To understand the mechanism of the inhibitory action of these two isomers on bone resorption we investigated the effects of 1α,25-(OH)23-26,23-lactone on unfractionated mouse bone marrow cells in vitro. The addition of 1α,25-(OH)2D3 to these cultures dose-dependently stimulated the formation of multinucleated cells over a range of 10-9-10-7 M. The 23(S),25(S)- and 23(R),25(R)-1α,25-(OH)2D3-26,23-lactones also increased the number of multinucleated cells, whereas the 23(S),25(R)- and 23(R),25(S)-1α,25-(OH)2D3-26,23-lactones failed to do so. In addition, these latter two diastereomers inhibited the 1α,25-(OH)2D3 stimulation of multinucleated cell formation, although the 23(S),25(S)- and 23(R),25(R)-1α,25-(OH)2D3-26,23-lactones and 24R,25-(OH)2D3 did not. These multinucleated cells responded to calcitonin and contained tartrate-resistant acid phosphatase, both of which are characteristic of osteoclasts. The present data suggest that inhibition of multinucleated cell formation is the mechanism by which the 23(S),25(R)- or 23(R),25(S)-1α,25-(OH)2D3-26,23-lactone inhibits bone resorption induced by 1α,25-(OH)2D3.",
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T1 - 1α,25-Dihydroxyvitamin D3[1α,25-(OH)2D3]-26,23-lactone inhibits 1,25-(OH)2D3-mediated fusion of mouse bone marrow mononuclear cells

AU - Ishizuka, S.

AU - Kurihara, Noriyoshi

AU - Hakeda, S.

AU - Maeda, N.

AU - Ikeda, K.

AU - Kumegawa, M.

AU - Norman, A. W.

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N2 - Vitamin D3 and its hormonally active metabolite 1,25-dihydroxyvitamin D3[1,25-(OH)2D3] can be metabolized to a number of daughter metabolites, including 1α,25-(OH)2D3-26,23-lactone; this latter compound has four diastereoisomers. The 23(S),25(R)-lactone (naturally occurring) and the 23(R),25(S)-1α,25-(OH)2D3-26,23-lactone are both known to be able to inhibit bone resorption induced by 1α,25-(OH)2D3 under in vivo or in vitro conditions. To understand the mechanism of the inhibitory action of these two isomers on bone resorption we investigated the effects of 1α,25-(OH)23-26,23-lactone on unfractionated mouse bone marrow cells in vitro. The addition of 1α,25-(OH)2D3 to these cultures dose-dependently stimulated the formation of multinucleated cells over a range of 10-9-10-7 M. The 23(S),25(S)- and 23(R),25(R)-1α,25-(OH)2D3-26,23-lactones also increased the number of multinucleated cells, whereas the 23(S),25(R)- and 23(R),25(S)-1α,25-(OH)2D3-26,23-lactones failed to do so. In addition, these latter two diastereomers inhibited the 1α,25-(OH)2D3 stimulation of multinucleated cell formation, although the 23(S),25(S)- and 23(R),25(R)-1α,25-(OH)2D3-26,23-lactones and 24R,25-(OH)2D3 did not. These multinucleated cells responded to calcitonin and contained tartrate-resistant acid phosphatase, both of which are characteristic of osteoclasts. The present data suggest that inhibition of multinucleated cell formation is the mechanism by which the 23(S),25(R)- or 23(R),25(S)-1α,25-(OH)2D3-26,23-lactone inhibits bone resorption induced by 1α,25-(OH)2D3.

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