Stimulation of RANKL and inhibition of membrane-type matrix metalloproteinase-1 expression by parathyroid hormone in normal human osteoblasts.
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.
Guo
Li-Juan
LJ
Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
Xie
Hui
H
Zhou
Hou-De
HD
Luo
Xiang-Hang
XH
Peng
Yi-Qun
YQ
Liao
Er-Yuan
EY
D000328:Adult; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D053504:Matrix Metalloproteinases, Membrane-Associated; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010281:Parathyroid Hormone; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases