IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae.
IL-6, leukemia inhibitory factor (LIF), and oncostatin M (OSM) are IL-6-type cytokines that stimulate osteoclast formation and function. In the present study, the resorptive effects of these agents and their regulation of receptor activator of NF-kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG) were studied in neonatal mouse calvaria. When tested separately, neither human (h) IL-6 nor the human soluble IL-6R (shIL-6R) stimulated bone resorption, but when hIL-6 and the shIL-6R were combined, significant stimulation of both mineral and matrix release from bone explants was noted. Semiquantitative RT-PCR showed that hIL-6 plus shIL-6R enhanced the expression of RANKL and OPG in calvarial bones, but decreased RANK expression. Human LIF, hOSM, and mouse OSM (mOSM) also stimulated 45Ca release and enhanced the mRNA expression of RANKL and OPG in mouse calvaria, but had no effect on the expression of RANK. In agreement with the RT-PCR analyses, ELISA measurements showed that both hIL-6 plus shIL-6R and mOSM increased RANKL and OPG proteins. 1,25-Dihydroxyvitamin D3 (D3) also increased the RANKL protein level, but decreased the protein level of OPG. OPG inhibited 45Ca release stimulated by RANKL, hIL-6 plus shIL-6R, hLIF, hOSM, mOSM, and D3. An Ab neutralizing mouse gp130 inhibited 45Ca release induced by hIL-6 plus shIL-6R. These experiments demonstrated stimulation of calvarial bone resorption and regulation of mRNA and protein expression of RANKL and OPG by D3 and IL-6 family cytokines as well as regulation of RANK expression in preosteoclasts/osteoclasts of mouse calvaria by D3 and hIL-6 plus shIL-6R.
Palmqvist
Py
P
Department of Oral Cell Biology, Umea University, Umea, Sweden.
Persson
Emma
E
Conaway
H Herschel
HH
Lerner
Ulf H
UH
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D001862:Bone Resorption / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D002132:Calcium Radioisotopes / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050822:Cytokine Receptor gp130; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology; D004338:Drug Combinations; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D015850:Interleukin-6 / Q000502:physiology*; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008024:Ligands; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D053683:Oncostatin M; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000378:metabolism; D053244:Osteoprotegerin; D010455:Peptides / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018121:Receptors, Cytokine / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000502:physiology; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D015703:Antigens, CD; D002132:Calcium Radioisotopes; D002352:Carrier Proteins; D004338:Drug Combinations; D006023:Glycoproteins; D006131:Growth Inhibitors; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D007106:Immune Sera; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008024:Ligands; D008222:Lymphokines; D008562:Membrane Glycoproteins; C508351:OSM protein, human; C508352:Osm protein, mouse; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018121:Receptors, Cytokine; D018160:Receptors, Cytoplasmic and Nuclear; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D002117:Calcitriol; D015232:Dinoprostone