Inhibin suppresses and activin stimulates osteoblastogenesis and osteoclastogenesis in murine bone marrow cultures
Inhibin suppresses and activin stimulates osteoblastogenesis and osteoclastogenesis in murine bone marrow cultures
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DOI：
10.1210/en.143.1.74
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发表时间：
2002-01-01
期刊：
影响因子：
4.8
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Gaddy-Kurten, D;Coker, JK;Manolagas, SC
利用原代小鼠骨髓细胞培养，我们证明抑制素抑制成骨细胞和破骨细胞的发生。相反，激活素支持成骨细胞形成（通过碱性磷酸酶阳性和矿化集落形成）；激活素也刺激破骨细胞的形成（通过染色测定抗酒石酸酸性磷酸酶阳性多核细胞）。抑制素、激活素拮抗剂卵泡抑素和骨形态发生蛋白拮抗剂noggin都能抑制骨髓培养中内源性激活素的积累。与激活素减少相关的是矿化成骨细胞集落形成的丧失（集落形成单位-成骨细胞；CFU-OB）。然而，外源性激活素管理，即使在noggin存在的情况下，允许碱性磷酸酶阳性和CFU-OB集落在体外形成。相反，局部产生的激活素对成骨细胞和破骨细胞发育的刺激作用不太可能超过性腺来源的抑制素的抑制作用。抑制素的抑制作用维持在激活素或骨形态发生蛋白存在的情况下，这表明存在一种不同的抑制素特异性受体。综上所述，抑制素和激活素在体外对成骨细胞和破骨细胞形成的直接调节表明，在围绝经期过渡期间，骨髓细胞检测到的抑制素/激活素比例的变化有助于改变细胞分化，并可能与此时观察到的骨吸收增加有关。
Using primary murine bone marrow cell cultures, we demonstrate that inhibin suppresses osteoblastogenesis and osteoclastogenesis. In contrast, activin supports osteoblast formation (by alkaline phosphatase-positive and mineralized colony formation); and activin also stimulates osteoclast formation (as measured by staining tartrate-resistant acid phosphatase-positive multinucleated cells). Inhibin, the activin antagonist follistatin, and the bone morphogenetic protein antagonist noggin can all suppress endogenous activin accumulation in bone marrow cultures. Associated with this decrease in activin is the loss of mineralized osteoblastic colony formation (colony forming unit-osteoblast; CFU-OB). However, exogenous activin administration, even in the presence of noggin, permits both alkaline phosphatase-positive and CFU-OB colony formation in vitro. In contrast, the stimulatory effects of locally produced activin on osteoblast and osteoclast development are not likely to be dominant over the suppressive effects of gonadally derived inhibin. The suppressive effect of inhibin is maintained in the presence of either activin or bone morphogenetic protein, suggesting the presence of a distinct inhibin-specific receptor. Taken together, the direct regulation of osteoblastogenesis and osteoclastogenesis by inhibin and activin in vitro suggest that changes in the inhibin/activin ratio detected by bone marrow cells, during the perimenopausal transition, contribute to altered cell differentiation and may be associated with the increased bone resorption observed at this time.