Experimental in vitro infection of rat osteoblasts with measles virus stimulates osteogenic differentiation

• Published in: Biochemical and biophysical research communications 2014-09, Vol.451 (4), p.609-614
• Main Authors: Ayala-Peña, V., Santillán, G., Scolaro, L.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Alkaline Phosphatase - biosynthesis; Animals; Bone and Bones - metabolism; Bone Morphogenetic Protein 4 - biosynthesis; Bone morphogenetic proteins; Cell Differentiation - drug effects; Cells, Cultured; Chromones - pharmacology; Differentiation; Measles virus; Measles virus - physiology; Morpholines - pharmacology; Osteoblasts; Osteoblasts - physiology; Osteoblasts - virology; Osteogenesis - physiology; Otosclerosis; Otosclerosis - etiology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Rats; Virus Replication
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.08.027

•Measles virus is able to infect rat osteoblasts in vitro.•Osteoblasts infected with measles virus express augmented levels of bone morphogenetic proteins.•Purinergic stimulation of bone morphogenetic proteins in osteoblasts is not additive to infection.•Stimulation by measles virus is not dependent on PI3K/AKT signalling pathway. 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.