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A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
A murine model of inflammatory bone disease
T A Hentunen1, S J Choi, B F Boyce
1Department of Medicine/Hematology, University of Texas Health Science Center, San Antonio, USA.
Abstract:
We have recently reported the identification of a new recessive mutation on murine chromosome 18 that results in tail kinks and deformity in the lower extremities of mice. Preliminary examination of the bones of these mice showed that there are abnormalities present that resembled chronic recurrent multifocal osteomyelitis. Accordingly, this new mutation was named "CMO." In this report, we describe the histology of bones in CMO mice, as well as the capacity of the bone marrow cells from these animals to form osteoclasts (OCLs). In addition, we tested conditioned media from non-adherent marrow cells and total marrow cells from CMO mice for their capacity to induce OCL formation in normal murine marrow cultures. These studies demonstrated that the bone disease in these animals is inflammatory in nature, and a soluble factor(s) that is not IL-1alpha, IL-6 or TNF-alpha is released by marrow cells from CMO animals and enhances OCL formation in normal murine marrow cultures.
Insights
A new mouse mutation, chronic recurrent multifocal osteomyelitis (CMO), causes bone deformities. Marrow cells from CMO mice release a factor that enhances osteoclast formation, indicating an inflammatory bone disease.
Area of Science:
- Genetics
- Immunology
- Skeletal Biology
Background:
- A novel recessive mutation on mouse chromosome 18 causes tail kinks and limb deformities.
- Preliminary bone examination revealed abnormalities resembling chronic recurrent multifocal osteomyelitis (CMO).
Purpose of the Study:
- To investigate the bone histology in CMO mice.
- To assess the osteoclast (OCL) formation capacity of bone marrow cells from CMO mice.
- To identify soluble factors from CMO marrow cells that influence OCL formation.
Main Methods:
- Histological analysis of bones from CMO mice.
- In vitro culture of bone marrow cells to assess osteoclastogenesis.
- Testing conditioned media from CMO marrow cells for osteoclast-inducing activity in normal murine marrow cultures.
Main Results:
- CMO mouse bone histology shows inflammatory bone disease.
- Marrow cells from CMO mice exhibit enhanced osteoclast formation capacity.
- Conditioned media from CMO marrow cells contain soluble factor(s) that promote osteoclastogenesis in normal marrow cultures.
Conclusions:
- The bone disease in CMO mice is inflammatory.
- A novel soluble factor, distinct from IL-1α, IL-6, or TNF-α, is released by CMO marrow cells.
- This factor contributes to enhanced osteoclast formation, driving the observed bone pathology.
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