Modulation of the effects of osteoprotegerin (OPG) ligand in a human leukemic cell line by OPG and calcitonin.
The discovery of osteoprotegerin (OPG), osteoprotegerin ligand (OPGL), and RANK has elucidated the mechanism by which osteoblasts and stromal cells regulate osteoclastic differentiation and function and mediate the effects exerted by other hormones and cytokines. We have investigated the effects of these novel cytokines on the preosteoclastic cell line FLG 29.1. We show that OPGL alone and in combination with macrophage colony-stimulating factor (CSF-1) dramatically reduced replication and increased tartrate-resistant acid phosphatase activity. However, although FLG29.1 cells appear to adhere to the bone surface, they are not able to form resorption lacunae. OPG and calcitonin completely abolished the differentiation induced by OPGL. RANK was detectable in FLG 29.1 and the number of positive cells was increased by OPGL/CSF-1 treatment while reduced by calcitonin. We propose that calcitonin could interact with the OPG/OPGL, and its effects on RANK may explain in part the action of this hormone in suppressing bone resorption.
Mancini
L
L
Division of Pharmacology, William Harvey Research Institute, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
Moradi-Bidhendi
N
N
Brandi
M L
ML
Perretti
M
M
MacIntyre
I
I
D000135:Acid Phosphatase / Q000378:metabolism; D002116:Calcitonin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000091344:Filaggrin Proteins; D006023:Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007948:Leukemia, Monocytic, Acute; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor; D002116:Calcitonin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase