title: GP130/OSMR is the only LIF/IL-6 family receptor complex to promote osteoblast differentiation of calvaria progenitors.
abstract: Leukemia inhibitory factor (LIF) and its receptor (LIFR) are "twins" of Oncostatin M (OSM) and OSMR, respectively, likely having arisen through gene duplications. We compared their effects in a bone nodule-forming model of in vitro osteogenesis, rat calvaria (RC) cell cultures. Using a dominant-negative LIF mutant (hLIF-05), we showed that in RC cell cultures mouse OSM (mOSM) activates exclusively glycoprotein 130 (gp130)/OSMR. In treatments starting at early nodule formation stage, LIF, mOSM, IL-11, and IL-6 + sIL-6R inhibit bone nodule formation, that is, osteoprogenitor differentiation. Treatment with mOSM, and no other cytokine of the family, in early cultures (day 1-3 or 1-4) increases bone colony numbers. hLIF-05 also dose dependently stimulates bone nodule formation, confirming the inhibitory action of gp130/LIFR on osteogenesis. In pulse treatments at successive stages of bone nodule formation and maturation, LIF blocks osteocalcin (OCN) expression by differentiated osteoblasts, but has no effect on bone sialoprotein (BSP) expression. Mouse OSM inhibits OCN and BSP expression in preconfluent cultures with no or progressively reduced effects at later stages, reflecting the disruption of early nodules, possibly due to the strong apoptotic action of mOSM in RC cell cultures. In summary, LIFR and OSMR display differential effects on differentiation and phenotypic expression of osteogenic cells, most likely through different signal transduction pathways. In particular, gp130/OSMR is the only receptor complex of the family to stimulate osteoprogenitor differentiation in the RC cell culture model.
authors.affiliation: INSERM U403, Lyon, France. luc.malaval@univ-st-etienne.fr
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
authors.forename: Fina
authors.initials: F
authors.lastname: Liu
authors.forename: Ann B
authors.initials: AB
authors.lastname: Vernallis
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D053683:Oncostatin M; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018121:Receptors, Cytokine / Q000502:physiology*; D019947:Receptors, Interleukin-6 / Q000502:physiology; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D006131:Growth Inhibitors; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; C494201:Il6st protein, rat; 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; C507842:Lifr protein, rat; D008562:Membrane Glycoproteins; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins; D053683:Oncostatin M; D050822:Cytokine Receptor gp130