Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease

We evaluated OCLs from 3 patients with Paget’s disease and determined that measles virus nucleocapsid protein was expressed in 70% of these OCLs

Jumpei Teramachi

2016

Scholarcy highlights

  • Paget’s disease is the most exaggerated example of coupled bone remodeling, with highly localized areas of increased bone resorption, accompanied by exuberant new bone formation
  • measles virus nucleocapsid protein was detectable in peripheral blood–derived OCLs from 2 patients who expressed MVNP in OCLs formed in marrow cultures and was not detectable in a PD patient who did not express MVNP
  • We cannot determine from our experiments whether all the circulating OCL precursors in MVNP-positive PD patients express MVNP or whether only a subpopulation of these precursors express MVNP
  • OCLs derived from p62P392L-harboring PD patients expressing MVNP had increased levels of ephrinB2
  • These results are consistent with our hypothesis that ephrinB2 increases new bone formation in PD patients expressing MVNP
  • EphB4-Fc treatment decreased IL-6 and IGF1 expression in these cocultures. These data support the hypothesis that increased ephrinB2/ EphB4 signaling induced by MVNP in OCLs plays a major role in coupling between bone resorption and new bone formation in PD and that suppressing OCL differentiation by inducing reverse signaling through ephrinB2 decreases the enhanced IL-6 and IGF1 production induced by MVNP expressions in OCLs
  • These results further suggest that enhanced coupling factor expression and increased IGF1 production by pagetic OCLs are major contributors to the rapid bone formation that occurs in Paget’s disease

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