A spontaneous model of spondyloarthropathies that develops bone loss and pathological bone formation: A process regulated by IL27RA-/- and mutant-p53

• Published in: PloS one Vol. 13; no. 3; p. e0193485
• Main Authors: Dibra, Denada, Xia, Xueqing, Gagea, Mihai, Lozano, Guillermina, Li, Shulin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2018; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Medicine and Health Sciences; Research and Analysis Methods
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193485

Spondyloarthropathies, the second most frequently occurring form of chronic inflammatory arthritis, affects young adults in particular. However, a proper model with which to study the biology of this disease and to develop therapeutics is lacking. One of the most accepted animal models for this disease uses HLA-B27/Hu-β2m transgenic rats; however, only 30%-50% of male HLA-B27/Hu-β2m rats develop spontaneous, clinically apparent spondylitis and have a variable time until disease onset. Here, we report a high-incidence, low-variation spontaneous mouse model that delineates how the combination of inflammatory cytokine interleukin-27 (IL-27) signaling deficiency and mitogenic signaling (mutant p53R172H) in vivo, leads to bone loss in the vertebral bodies and ossification of the cartilage in the intervertebral discs. In this human disease-like mouse model, bone loss and pathogenic bone development are seen as early as 4 months of age in the absence of inflammatory aggregates in the enthesis or intervertebral disc.