Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts
Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts
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DOI：
10.1677/joe.0.1700451
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发表时间：
2001-08-01
影响因子：
4
通讯作者：
Gardiner, EM
中科院分区：
文献类型：
--
作者：
Thomas, GP;Baker, SUK;Gardiner, EM
成骨细胞-破骨细胞协调在维持骨骼完整性中至关重要。成骨细胞谱系的未成熟细胞对破骨细胞生成的调节通过NF κ B（RANK）受体激活剂、其配体RANKL和骨保护素（OPG）（RANKL的天然诱饵受体）介导。在此，研究了小鼠成骨细胞培养物中OPG和RANKL的表达，以确定破骨细胞生成刺激是否依赖于成骨细胞分化的阶段和促钙激素1，25-二羟维生素D-3的存在（1.25-（OH）（2）D-3）.相对于不太成熟的培养物，矿化开始后成骨细胞培养物中OPG mRNA表达增加，但对1，25-（OH）（2）D-3处理没有反应。相比之下，基础RANKL mRNA表达在分化过程中没有变化，但在所有时间均被1，25-（OH）（2）D-3处理显著增强。然而，在更成熟的培养物中，1，25-（OH）（2）D-3对RANKL的刺激作用减弱。因此，RANKL/OPG比值（破骨细胞生成刺激的指数）在成骨细胞分化的所有阶段均通过1，25-（OH）（2）D-3处理增加，但在矿化开始后的培养物中增加程度较小。因此，1，25-（OH）（2）D-3驱动的未成熟成骨细胞破骨细胞生成潜力的增加似乎是由RANKL mRNA表达增加介导的，而成熟成骨细胞由于OPG mRNA表达增加而具有相对降低的破骨细胞生成活性。这些研究结果表明，最近提出的成熟成骨细胞对破骨细胞生成的负调节作用的可能机制，并表明，在局部微环境中的未成熟和成熟成骨细胞的相对比例可能控制在每个特定的骨部位的吸收程度。
Osteoblast-osteoclast coordination is critical in the maintenance of skeletal integrity The modulation of osteoclastogenesis by immature cells of the osteoblastic lineage is mediated through receptor activator of NF kappaB (RANK), its ligand RANKL, and osteoprotegerin (OPG), a natural decoy receptor for RANKL. Here, the expression of OPG and RANKL in primary mouse osteoblastic cultures was investigated to determine whether the osteoclastogenic stimulus depended on the stage of osteoblastic differentiation and the presence of the calciotrophic hormone 1,25-dihydroxvitamin D-3 (1.25-(OH)(2)D-3).OPG mRNA expression was increased in osteoblastic cultures after the onset of mineralisation relative to less mature cultures, but did not alter in response to 1,25-(OH)(2)D-3 treatment. In contrast, basal RANKL mRNA expression did not change during differentiation but was significantly enhanced by 1,25-(OH)(2)D-3 treatment at all times. The stimulatory effects of 1,25-(OH)(2)D-3 on RANKL were lessened in more mature cultures, however. The RANKL/OPG ratio, an index of osteoclastogenic stimulus, was therefore increased by 1,25-(OH)(2)D-3 treatment at all stages of osteoblastic differentiation, but to a lesser degree in cultures after the onset of mineralisation. Thus the 1,25-(OH)(2)D-3-driven increase in osteoclastogenic potential of immature osteoblasts appears to be mediated by increased RANKL mRNA expression, with mature osteoblasts having relatively decreased osteoclastogenic activity due to increased OPG mRNA expression. These findings suggest a possible mechanism for the recently proposed negative regulatory role of mature osteoblasts on osteoclastogenesis and indicate that the relative proportions of immature and mature osteoblasts in the local microenvironment may control the degree of resorption at each specific bone site.