Stimulation of RANKL and Inhibition of Membrane-Type Matrix Metalloproteinase-1 Expression by Parathyroid Hormone in Normal Human Osteoblasts.

Receptor activator of NF-κB(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. [ABSTRACT FROM AUTHOR]