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  • 1
    ISSN: 1432-0827
    Keywords: Bone resorption ; Osteoclast-like cell formation ; Bone Ca mobilization ; Intestinal Ca transport ; 24R,25-dihydroxy-26,27-dimethylvitamin D3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract To determine the possibility that methyl substitution in 26- and 27-positions of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] alters activities of the original compound, the effects of 24,25(OH)2D3 on calcium (Ca) regulating activity were compared with those of its methyl analog [24,25(OH)2(CH3)2D3] in addition to 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 24,25(OH)2D3 at 10-6 M and 24,25(OH)2(CH3)2D3 at 10-7 M and above significantly stimulated both bone resorption in neonatal mouse calvaria cultures and formation of osteoclast-like multinucleated cells (MNC) in mouse bone marrow cultures. A stimulative effect of 1,25(OH)2D3 on bone resorption and MNC formation was recognized in very low concentrations (10-11 M and above). Although a potency of 24,25(OH)2(CH3)2D3 in stimulating bone calcium (Ca) mobilization and intestinal Ca transport was higher than that of 24,25(OH)2D3, the potencies of both compounds were similar to that of 1,25(OH)2D3 unlike in vitro experiments. As 1,24R,25-trihydroxy-26,27-dimethylvitamin D3 showed almost the same effect as 24,25(OH)2(CH3)2D3, the dihydroxy form is suggested to be hydroxylated at 1α position and converted to trihydroxy form in vitamin D-deficient rats. From these results, methyl substitution in 26- and 27-position of 24,25(OH)2D3 was found to elevate Ca regulating activity of the original compound. In addition, it is suggested that the basis for a similarity in potency between 1,25(OH)2D3 and 24,25(OH)2D3 or its dimethyl analog in vitamin D-deficient rats is likely the result of 1 α-hydroxylation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0827
    Keywords: Bone resorption ; Osteoclast formation ; Resorption lacunae ; 24-epi-1α-hydroxyvitamin D2 ; 24-epi-1α,25-dihydroxyvitamin D2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Bone-resorbing activities of 24-epi-1α-hydroxyvitamin D2 [24-epi-1α(OH)D2], 24-epi-1α,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2], and 1α,24S,25-trihydroxyvitamin D2 [1,24S,25(OH)3D2], which might be a metabolite of 24-epi-1,25(OH)2D2, were investigated. In an in vitro bone resorption test, the activity of 24-epi-1α(OH)D2 was similar to that of 1α-hydroxyvitamin D3 [1α(OH)D3] at 10-9 M-10-6 M. The activity of 24-epi-1,25(OH)2D2 was weaker than that of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] at 10-11 M-10-8 M. On the other hand, the activity of 1,24S,25(OH)3D2 was similar to that of 24-epi-1,25(OH)2D2 at 10-11 M-10-9 M. In the formation assay of osteoclast-like cells, the activity of 24-epi-1α(OH)D2 was weaker than that of 1α(OH)D3 at 10-7 M. The activity of 24-epi-1,25(OH)2D2 was almost similar to that of 1,25(OH)2D3 at 10-11 M-10-7 M. The activity of 1,24S,25(OH)3D2 was significantly weaker than that of 24-epi-1,25(OH)2D2 at 10-11 M-10-9 M. In the two experiments, the potencies of 24-epi-1,25(OH)2D2 were about 100 times higher than those of 24-epi-1α(OH)D2. In an in vivo/in vitro bone resorption test, the activity of 24-epi-1α(OH)D2 was almost similar to those of 1α(OH)D3 and 1,25(OH)2D3 and higher than those of 24-epi-1,25(OH)2D2 and 1,24S,25(OH)3D2. 24-epi-1α-(OH)D2 and 1α(OH)D3 were longer lasting than 24-epi-1,25(OH)2D2 and 1,25(OH)2D3 in this experiment. These results suggested that 24-epi-1α(OH)D2 as well as 1α(OH)D3 was converted into dihydroxy form in vivo.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0827
    Keywords: Lead ; Prostaglandin E2 ; Osteoclast-like cell formation ; Mouse bone marrow cells ; Cyclic adenosine 3′,5′-monophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2–10 μM, whereas at 40 μM Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 μM Pb and decreased with increasing concentration of Pb at 10–40 μM. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E2 (PGE2) receptor. Pb stimulated the production of PGE2 in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE2. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2′,5′-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE2-induced increase in the levels of cyclic adenosine 3′,5′-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE2 which increases the intracellular levels of cAMP and calcium ions.
    Type of Medium: Electronic Resource
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