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  • 1
    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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  • 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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