Effect of corticosteroids on human osteoclast formation and activity
Effect of corticosteroids on human osteoclast formation and activity
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DOI：
10.1677/joe.0.1750155
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发表时间：
2002-10-01
影响因子：
4
通讯作者：
Athanasou, NA
中科院分区：
文献类型：
--
作者：
Hirayama, T;Sabokbar, A;Athanasou, NA
已知慢性皮质类固醇治疗可诱导骨丢失和骨质疏松症。破骨细胞是由单核吞噬细胞前体形成的专门的骨吸收细胞，单核吞噬细胞前体在单核细胞部分中循环。在这项研究中，我们研究了合成糖皮质激素，地塞米松，对人破骨细胞的形成和骨吸收活性的影响。在存在和不存在地塞米松（10（-8）M）的情况下，将人单核细胞在盖玻片和牙本质切片上与核因子κ B配体的可溶性受体激活剂（RANKL; 30 ng/ml）和人巨噬细胞集落刺激因子（M-CSF; 25 ng/ml）培养长达21天。在培养单核细胞（在此期间主要发生细胞增殖和分化）的7天和14天期间添加地塞米松导致抗酒石酸盐酸性磷酸酶阳性多核细胞的形成显著增加，并增加腔隙性吸收。与未添加地塞米松的培养物相比，14天后（破骨细胞的吸收活性开始时）向单核细胞培养物中添加地塞米松降低了腔隙性吸收的程度。从骨巨细胞瘤中分离的破骨细胞中加入地塞米松可显著抑制骨吸收陷窝的形成。我们的研究结果表明，地塞米松对破骨细胞的形成和活性有直接影响，刺激人破骨细胞前体细胞的增殖和分化，并抑制成熟破骨细胞的骨吸收活性。
Chronic corticosteroid treatment is known to induce bone loss and osteoporosis. Osteoclasts are specialised bone-resorbing cells that are formed from mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have examined the effect of the synthetic glucocorticoid, dexamethasone, on human osteoclast formation and bone-resorbing activity. Human monocytes were cultured for up to 21 days on glass coverslips and dentine slices, with soluble receptor activator for nuclear factor kappaB ligand (RANKL; 30 ng/ml) and human macrophage-colony stimulating factor (M-CSF; 25 ng/ml) in the presence and absence of dexamethasone (10(-8) M). The addition of dexamethasone over a period of 7 and 14 days of culture of monocytes (during which cell proliferation and differentiation predominantly occurred) resulted in a marked increase in the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and an increase in lacunar resorption. The addition of dexamethasone to monocyte cultures after 14 days (when resorptive activity of osteoclasts had commenced) reduced the extent of lacunar resorption compared with cultures to which no dexamethasone had been added. The addition of dexamethasone to osteoclasts isolated from giant cell tumours of bone significantly inhibited resorption pit formation. Our findings indicate that dexamethasone has a direct effect on osteoclast formation and activity, stimulating the proliferation and differentiation of human osteoclast precursors and inhibiting the bone-resorbing activity of mature osteoclasts.