Guo Li-Juan, Xie Hui, Zhou Hou-De, Luo Xiang-Hang, Peng Yi-Qun, Liao Er-Yuan
Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
Endocr Res. 2004 Aug;30(3):369-77. doi: 10.1081/erc-200033719.
Receptor activator of NF-kappaB (RANK) ligand (RANKL), expressed by cells of the osteoblast lineage binds to RANK, induces signaling and a gene expression cascade that leads to osteoclast differentiation and activation. Recently, osteoblast-derived membrane-type matrix metalloproteinases-1 (MT1-MMP) have been implicated in the process of bone resorption by degrading bone matrix. In the present study, we investigated the effects of parathyroid hormone [PTH (1-34)] on RANKL and MT1-MMP production in cultured normal human osteoblast-like cells (hOB). In reverse transcription polymerase chain reaction studies, we observed that PTH (1-34) induced RANKL messenger ribonucleic acid (mRNA) expression. Activity assays demonstrated that PTH (1-34) simultaneously inhibited MT1-MMP protein expression in a dose- and time-dependent manner. The effect of PTH (1-34) on MT1-MMP production was parallel to that on RANKL expression, suggesting a tight inverse relationship between MT1-MMP and RANKL expression. Our findings indicated that the decreased MT1-MMP expression by PTH may be involved in RANKL signaling in osteoblasts and activation of osteoclasts.
核因子κB受体激活剂（RANK）配体（RANKL）由成骨细胞系细胞表达，与RANK结合，诱导信号传导和基因表达级联反应，导致破骨细胞分化和激活。最近，成骨细胞衍生的膜型基质金属蛋白酶-1（MT1-MMP）通过降解骨基质参与骨吸收过程。在本研究中，我们研究了甲状旁腺激素[PTH（1-34）]对培养的正常人成骨样细胞（hOB）中RANKL和MT1-MMP产生的影响。在逆转录聚合酶链反应研究中，我们观察到PTH（1-34）诱导RANKL信使核糖核酸（mRNA）表达。活性测定表明，PTH（1-34）以剂量和时间依赖性方式同时抑制MT1-MMP蛋白表达。PTH（1-34）对MT1-MMP产生的影响与对RANKL表达的影响平行，表明MT1-MMP与RANKL表达之间存在紧密的负相关关系。我们的研究结果表明，PTH降低MT1-MMP表达可能参与成骨细胞中的RANKL信号传导和破骨细胞的激活。
