title: Long term oncostatin M treatment induces an osteocyte-like differentiation on osteosarcoma and calvaria cells.
abstract: Previous in vitro studies on primary osteoblastic and osteosarcoma cells (normal and transformed osteoblasts) have shown that oncostatin M (OSM), a member of the interleukin-6 family, possesses cytostatic and pro-apoptotic effects in association with complex and poorly understood activities on osteoblast differentiation. In this study, we use rat osteosarcoma cells transduced with lentiviral particles encoding OSM (lvOSM) to stably produce this cytokine. We show that after several weeks of culture, transduced OSRGA and ROS 17/2.8 cells are growth inhibited and sensitized to apoptosis induced by the kinase inhibitor Staurosporine (Sts). Moreover, this long term OSM treatment induces (i) a decrease in osteoblastic markers, (ii) morphological changes leading to an elongated and/or stellate shape and (iii) an increase in osteocytic markers (sclerostin and/or E11), suggesting an osteocyte-like differentiation. We also show that non transformed rat calvaria cells transduced with lvOSM differentiate into stellate shaped cells expressing sclerostin, E11, Phex and functional hemichannels. Together, these results indicate that osteosarcoma cells stably producing OSM do not develop resistance to this cytokine and thus could be a valuable new tool to study the anti-cancer effect of OSM in vivo. Moreover, OSM-over-expressing osteoblastic cells differentiate into osteocyte-like cells, the major cellular contingent in bone, providing new culture conditions for this cell type which is difficult to obtain in vitro.
authors.affiliation: INSERM, ERI 7, Nantes, F-44035, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Brounais
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: David
authors.forename: Céline
authors.initials: C
authors.lastname: Chipoy
authors.forename: Valérie
authors.initials: V
authors.lastname: Trichet
authors.forename: Virginie
authors.initials: V
authors.lastname: Ferré
authors.forename: Céline
authors.initials: C
authors.lastname: Charrier
authors.forename: Laurence
authors.initials: L
authors.lastname: Duplomb
authors.forename: Martine
authors.initials: M
authors.lastname: Berreur
authors.forename: Françoise
authors.initials: F
authors.lastname: Rédini
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanchard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D016086:Lentivirus / Q000235:genetics; D053683:Oncostatin M / Q000235:genetics / Q000502:physiology*; D010011:Osteocytes / Q000166:cytology* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D012886:Skull / Q000166:cytology* / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053683:Oncostatin M; D053148:Caspase 3; D019311:Staurosporine