Abstract
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.
Acknowledgments
This work was supported by Grant‐30200322 from China National Natural Scientific Foundation, and A Foundation for the Author of National Excellent Doctoral Dissertation of PR China (200259). We are indebted to Professor Eleanor J. Mackie from the Department of Veterinary Science, University of Melbourne, Melbourne, Australia, for her kind suggestions and manuscript review.