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Published on: August 25, 2020
Experimental in vitro infection of rat osteoblasts with measles virus stimulates osteogenic differentiation
V Ayala-Peña1, G Santillán1, L Scolaro2
1Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, (B8000ICN) Bahía Blanca, Argentina.
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.
Insights
Measles virus (MeV) infects rat osteoblastic lineage cells (OBCs), promoting their differentiation. This viral infection of bone cells may play a role in bone disease development.
Area of Science:
- Virology
- Cell Biology
- Bone Biology
Background:
- Measles virus (MeV) is a significant human pathogen.
- Osteoblastic lineage cells (OBCs) are crucial for bone formation and remodeling.
- The interplay between viral infections and bone cell differentiation is not fully understood.
Purpose of the Study:
- To investigate the effects of measles virus (MeV) infection on primary rat osteoblastic lineage cells (OBCs).
- To determine the impact of MeV infection on osteoblast differentiation and maturation markers.
- To explore the role of specific signaling pathways (PI3K/AKT) and ATP in MeV infection and osteoblast differentiation.
Main Methods:
- Primary cultures of rat OBCs were infected with MeV.
- Viral titers and infectivity were measured.
- Expression levels of osteogenic differentiation markers (ALP, BSP, BMPs) were analyzed using mRNA analysis.
- Cells were treated with PI3K/AKT inhibitor (Ly294002) and ATPγS to assess their effects on viral replication and differentiation.
Main Results:
- MeV efficiently infected OBCs, releasing high titers of infectivity.
- MeV infection significantly increased the expression of osteogenic differentiation markers (2-75-fold).
- Pre-differentiation of OBCs influenced the stimulatory effect of MeV; PI3K/AKT inhibition increased viral titers, while ATPγS diminished MeV multiplication, without altering the induction of differentiation markers.
Conclusions:
- Measles virus can infect osteoblasts in vitro, promoting osteoblastic differentiation.
- This finding provides the first evidence linking MeV infection to osteoblast differentiation.
- The study suggests a potential role for MeV in bone pathogenic processes, such as otosclerosis.
