Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells.
The osteoclastogenic factor of osteoblastic origin has recently been elucidated as a novel Tumor Necrosis Factor (TNF)-ligand family member, termed osteoclast differentiation factor (ODF). Using a semiquantitative RT-PCR approach, we sought to determine the mRNA expression of ODF and its decoy receptor, osteoprotegerin (OPG), in a selection of osteoblastic cell lines and in response to three factors representative of different signal transduction pathways, vitamin D receptor, protein kinase A or gp130. Each osteotropic agent, either 1,25-(OH)2D3, PTH or IL-11, promoted an increase in the ratio of ODF:OPG, with maximal stimulation occurring at 24 h, 4 h, and 8 h, respectively, and furthermore each was shown to act in a dose-dependent manner. This report establishes that osteoblastic cell lines incapable of supporting osteoclast formation have markedly reduced ODF expression and also illustrates the importance of the relative abundance of ODF compared with the levels of OPG for the induction of osteoclastogenesis.
Horwood
N J
NJ
St. Vincent's Institute of Medical Research and The University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
Elliott
J
J
Martin
T J
TJ
Gillespie
M T
MT
D000818:Animals; D000831:Animals, Newborn; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D006023:Glycoproteins / Q000494:pharmacology*; D017370:Interleukin-11 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000494:pharmacology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018167:Receptors, Calcitriol / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects*
D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D017370:Interleukin-11; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D002117:Calcitriol