Understanding Coupling between Bone Resorption and Formation Are Reversal Cells the Missing Link?
Understanding Coupling between Bone Resorption and Formation Are Reversal Cells the Missing Link?
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DOI：
10.1016/j.ajpath.2013.03.006
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发表时间：
2013-07-01
影响因子：
6
通讯作者：
Delaisse, Jean-Marie
中科院分区：
文献类型：
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作者：
Andersen, Thomas L.;Abdelgawad, Mohamed E.;Delaisse, Jean-Marie
骨重建需要破骨细胞的骨吸收，成骨细胞的骨形成，以及一个鲜为人知的将吸收与形成相耦合的逆转阶段。反转期的可能参与者是被重新招募到破骨细胞腾出的陷窝中的细胞，并推测这些陷窝为骨形成做准备。这些细胞在这里被称为逆转细胞，覆盖了80%的侵蚀表面，但它们的性质尚不清楚，也不知道这些细胞的故障是否会导致绝经后骨质疏松症等疾病的骨质疏松症。在这里，我们结合了组织形态计量学和免疫组织化学在人的髂骨活检标本上，发现逆转细胞对通常由成骨细胞表达的因子具有免疫反应性，但不对单核细胞标志物具有免疫反应性。此外，逆转细胞的亚群显示出几个明显的特征，表明细胞处于停滞的生理状态。其发生率与绝经后骨质疏松症患者的骨小梁体积、类骨质和成骨细胞表面的减少有关。然而，它们在原发性甲状旁腺功能亢进症中几乎是不存在的，在这种甲状旁腺机能亢进症中，骨吸收和骨形成之间的转换发生得最好。总体而言，我们的观察表明，停滞的逆转细胞反映了流产的重塑周期，没有进展到骨形成步骤。因此，我们认为绝经后骨质疏松症的骨丢失不仅是由于通常认为的骨形成步骤的失败，而且也是由于反转步骤的失败。
Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone toss in diseases such as postmenopausal osteoporosis. Herein, we combined histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested physiological status. Their prevalence correlated with decreased trabecular bone volume and osteoid and osteoblast surfaces in postmenopausal osteoporosis. They were, however, virtually absent in primary hyperparathyroidism, in which the transition between bone resorption and formation occurs optimally. Collectively, our observations suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. We, therefore, propose that bone loss in postmenopausal osteoporosis does not only result from a failure of the bone formation step, as commonly believed, but also from a failure at the reversal step.