Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow - Evidence for autonomy from factors released during bone resorption
Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow - Evidence for autonomy from factors released during bone resorption
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DOI：
10.1172/jci1039
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发表时间：
1998-05-01
影响因子：
15.9
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Jilka, RL;Takahashi, K;Manolagas, SC
性类固醇的丧失会导致骨吸收和骨形成同时增加，且前者超过后者。基于雌激素丢失后骨吸收增加是由于破骨细胞生成增加所致的证据，我们假设雌激素丢失也会刺激成骨细胞生成。我们报告称，在卵巢切除术后 2 至 8 周内，小鼠骨髓中间充质成骨细胞祖细胞的数量增加了 2 至 3 倍，并在 16 周时恢复到对照水平。循环骨钙素以及破骨细胞生成和骨质流失率遵循非常相似的时间模式。通过给予双膦酸盐阿仑膦酸盐抑制骨吸收导致成骨细胞祖细胞绝对数量减少；但不影响卵巢切除对成骨细胞或破骨细胞生成的刺激作用。这些观察结果表明，雌激素丧失后骨形成的增加可以至少部分地通过成骨细胞生成的增加来解释。此外，他们强烈建议，与正常的骨重塑不同，在破骨细胞吸收过程中，成骨细胞的发育是由骨基质释放的因子刺激的，雌激素缺乏会释放信号，以一种独立于骨吸收产生的需要的方式刺激成骨细胞祖细胞的分化，因此是不适当的。
Loss of sex steroids causes an increase in both the resorption and formation of bone, with the former exceeding the latter. Based on evidence that the increased bone resorption after estrogen loss is due to an increase in osteoclastogenesis, we hypothesized that estrogen loss also stimulates osteoblastogenesis. We report that the number of mesenchymal osteoblast progenitors in the murine bone marrow was increased two- to threefold between 2 and 8 wk after ovariectomy and returned to control levels by 16 wk. Circulating osteocalcin, as well as osteoclastogenesis and the rate of bone loss, followed a very similar temporal pattern. Inhibition of bone resorption by administration of the bisphosphonate alendronate led to a decrease of the absolute number of osteoblast progenitors; however, it did not influence the stimulating effect of ovariectomy on osteoblastogenesis or osteoclastogenesis. These observations indicate that the increased bone formation that follows loss of estrogen can be explained, at least in part, by an increase in osteoblastogenesis. Moreover, they strongly suggest that unlike normal bone remodeling, whereby osteoblast development is stimulated by factors released from the bone matrix during osteoclastic resorption, estrogen deficiency unleashes signals that can stimulate the differentiation of osteoblast progenitors in a fashion that is autonomous from the need created by bone resorption, and therefore, inappropriate.