title: Experimental in vitro infection of rat osteoblasts with measles virus stimulates osteogenic differentiation.
abstract: In this work we characterized the infection of a primary culture of rat osteoblastic lineage cells (OBCs) with measles virus (MeV) and the effect of infection on cell differentiation and maturation. Infection of OBCs with MeV led to high titers of infectivity released early after infection. Also, analysis of mRNAs corresponding to osteogenic differentiation markers like alkaline phosphatase (ALP), bone sialo-protein (BSP) and bone morphogenetic proteins (BMPs) 1-4-5-7 in OBCs revealed higher values (2-75-fold of increment) for infected cells in comparison with uninfected controls. Differentiation of OBCs in osteogenic medium prior to infection influenced the level of stimulation induced by MeV. Furthermore, treatment of OBCs with Ly294002, a PI3K/AKT inhibitor, increased viral titers, whereas treatment with 10μM or 100μM ATPγS diminished MeV multiplication. In addition, increments of osteogenic differentiation markers induced by MeV infection were not modified either by treatment with Ly294002 or ATPγS. These data provide the first evidence demonstrating that MeV can infect osteoblasts in vitro leading to osteoblastic differentiation, a key feature in bone pathogenic processes like otosclerosis.
authors.affiliation: Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, (B8000ICN) Bahía Blanca, Argentina.
authors.forename: V
authors.initials: V
authors.lastname: Ayala-Peña
authors.affiliation: Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, (B8000ICN) Bahía Blanca, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Santillán
authors.affiliation: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, Buenos Aires 1428, Argentina. Electronic address: luisco@qb.fcen.uba.ar.
authors.forename: L
authors.initials: L
authors.lastname: Scolaro
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D008459:Measles virus / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D010006:Osteoblasts / Q000502:physiology / Q000821:virology*; D010012:Osteogenesis / Q000502:physiology*; D010040:Otosclerosis / Q000209:etiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D014779:Virus Replication
chemical_list: D055415:Bone Morphogenetic Protein 4; D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase
keywords: Bone morphogenetic proteins; Differentiation; Measles virus; Osteoblasts; Otosclerosis