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.