Experimental models of Paget's disease

Area of Science:

• Bone biology
• Genetics
• Pathology

Background:

• Paget's disease (PD) is a bone remodeling disorder with unknown etiology.
• A viral cause for PD is suspected, linked to measles virus nucleocapsid (MVNP) in osteoclasts (OCLs).
• In vitro studies show MVNP gene transfection in OCL precursors induces a pagetic phenotype.

Purpose of the Study:

• To investigate the in vivo effects of MVNP expression in OCLs.
• To determine if MVNP expression in OCLs can induce a Paget's disease-like phenotype in mice.

Main Methods:

• Targeted MVNP gene expression to the OCL lineage in transgenic mice using the TRACP promoter.
• Conducted histomorphometric analysis and ex vivo marrow cultures.

Main Results:

• MVNP transgenic mice exhibited increased OCL and osteoblast (OBL) perimeter, elevated cancellous bone volume, and woven bone formation.
• Bone volume increased in MVNP mice from 3 to 12 months, unlike wildtype mice.
• OCLs from MVNP mice showed increased numbers, hyper-responsiveness to 1,25(OH)(2)D(3), and enhanced bone resorption capacity.

Conclusions:

• In vivo expression of MVNP in OCLs induces a bone phenotype characteristic of Paget's disease.
• This study provides in vivo evidence supporting a viral etiology for Paget's disease.