Premium
Impairment of Bone Remodeling in LIGHT/TNFSF14 ‐Deficient Mice
Author(s) -
Brunetti Giacomina,
Faienza Maria Felicia,
Colaianni Graziana,
Gigante Isabella,
Oranger Angela,
Pignataro Paolo,
Ingravallo Giuseppe,
Di Benedetto Adriana,
Bortolotti Sara,
Di Comite Mariasevera,
Storlino Giuseppina,
Lippo Luciana,
WardKavanagh Lindsay,
Mori Giorgio,
Reseland Janne E,
Passeri Giovanni,
Schipani Ernestina,
Tamada Koji,
Ware Carl F,
Colucci Silvia,
Grano Maria
Publication year - 2018
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3345
Subject(s) - osteoprotegerin , osteoclast , bone remodeling , medicine , cytokine , tumor necrosis factor alpha , endocrinology , osteoblast , proinflammatory cytokine , bone resorption , immune system , bone cell , cd8 , cancellous bone , immunology , inflammation , chemistry , pathology , receptor , biochemistry , activator (genetics) , in vitro
Multiple cytokines produced by immune cells induce remodeling and aid in maintaining bone homeostasis through differentiation of bone‐forming osteoblasts and bone‐resorbing osteoclasts. Here, we investigate bone remodeling controlled by the tumor necrosis factor (TNF) superfamily cytokine LIGHT. LIGHT ‐deficient mice ( Tnfsf14 ‐/‐ ) exhibit spine deformity and reduced femoral cancellous bone mass associated with an increase in the osteoclast number and a slight decrease of osteoblasts compared with WT mice. The effect of LIGHT in bone cells can be direct or indirect, mediated by both the low expression of the anti‐osteoclastogenic osteoprotegerin (OPG) in B and T cells and reduced levels of the pro‐osteoblastogenic Wnt10b in CD8 + T cells in Tnfsf14 ‐/‐ mice. LIGHT stimulation increases OPG levels in B, CD8 + T, and osteoblastic cells, as well as Wnt10b expression in CD8 + T cells. The high bone mass in Light and T‐ and B‐cell‐deficient mice ( Rag ‐ /Tnfsf14 ‐ ) supports the cooperative role of the immune system in bone homeostasis. These results implicate LIGHT as a potential target in bone disease. © 2017 American Society for Bone and Mineral Research.