The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated
The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated
复制标题
DOI：
10.1210/en.141.12.4768
复制
发表时间：
2000-12-01
期刊：
影响因子：
4.8
通讯作者：
Riggs, BL
中科院分区：
文献类型：
--
作者：
Gori, F;Hofbauer, LC;Riggs, BL
在骨重建过程中，决定骨吸收和形成的强制性顺序的一个或多个分子机制尚不清楚。RANK配体(RANK-L)是破骨细胞形成所必需的，其活性被可溶性诱骗受体--骨保护素(OPG)所中和。因为这两种分子都是由成骨细胞系细胞产生的，所以我们在条件永生化的人骨髓基质(HMS[2-15])细胞系中研究了它们的发育规律。这些细胞可以模拟从未分化前体(S)到具有完整成骨细胞表型的能够形成矿化结节的细胞的完整发育序列。在成骨细胞分化过程中，RANK-L信使RNA水平下降了5倍，而OPG信使RNA水平上升了7倍，导致RANK-L/OPG比率变化了35倍。OPG蛋白也增加了6倍。小鼠骨髓细胞在与未分化的HMS(2-15)细胞共培养时产生破骨细胞样细胞，但在不同分化阶段与HMS(2-15)细胞共培养时不产生破骨细胞样细胞，除非加入过量的RANK-L。因此，未分化的骨髓基质细胞具有较高的等级-L/骨保护素比率，可以启动和支持破骨细胞的形成，但在分化为成熟的成骨细胞表型后，它们不能。我们推测，基质/成骨细胞对OPG和RANK-L产生的发育心理调节有助于破骨细胞和成骨细胞在骨重建周期中的协调分化。
The one or more molecular mechanisms that determine the obligatory sequence of resorption followed by formation during bone remodeling is unclear. RANK ligand (RANK-L) is an essential requirement for osteoclastogenesis, and its activity is neutralized by binding to the soluble decoy receptor, osteoprotegerin (OPG). Because both molecules are produced by osteoblast lineage cells, we studied their developmental regulation in a conditionally immortalized human marrow stromal (hMS[2-15]) cell line. These cells can simulate the complete developmental sequence from undifferentiated precursor(s) to cells with the complete osteoblast phenotype that are capable of forming mineralized nodules. During osteoblast differentiation, RANK-L messenger RNA levels decreased by 5-fold, whereas OPG messenger RNA levels increased by 7-fold, resulting in a 35-fold change in the RANK-L/OPG ratio. OPG protein also increased by 6-fold. Mouse hone marrow cells generated osteoclast-like cells in coculture with undifferentiated hMS(2-15) cells, but did not when cocultured with hMS(2-15) cells in varying stages of differentiation, unless an excess of RANK-L was added. Thus, undifferentiated marrow stromal cells with a high RANK-L/OPG ratio can initiate and support osteoclastogenesis, but after differentiation to the mature osteoblast phenotype, they cannot. We speculate that the develop mental regulation of OPG and RANK-L production by stromal/osteoblast cells contributes to the coordinated sequence of osteoclast and osteoblast differentiation during the hone remodeling cycle.