TY - JOUR
T1 - A spontaneous model of spondyloarthropathies that develops bone loss and pathological bone formation
T2 - A process regulated by IL27RA-/- and mutant-p53
AU - Dibra, Denada
AU - Xia, Xueqing
AU - Gagea, Mihai
AU - Lozano, Guillermina
AU - Li, Shulin
N1 - Funding Information:
This work was supported by National Cancer Institute grant R01 CA120985 to SL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are thankful to Keith Michel for offering his technical expertise in micro- CT images. This study was supported by NIH R01 CA120985.
Publisher Copyright:
© 2018 Dibra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0193485
DO - 10.1371/journal.pone.0193485
M3 - Article
C2 - 29494633
AN - SCOPUS:85042908593
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 3
M1 - e0193485
ER -