Impairment of Bone Remodeling in LIGHT/TNFSF14-Deficient Mice

J Bone Miner Res. 2018 Apr;33(4):704-719. doi: 10.1002/jbmr.3345. Epub 2017 Dec 11.


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.


Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Bone Remodeling / genetics
  • Bone Remodeling / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cancellous Bone / immunology*
  • Cancellous Bone / pathology
  • Femur / immunology*
  • Femur / physiology
  • Mice
  • Mice, Knockout
  • Osteoblasts / immunology
  • Osteoclasts / immunology
  • Osteoclasts / pathology
  • Osteoprotegerin / genetics
  • Osteoprotegerin / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / deficiency*
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / immunology
  • Wnt Proteins / genetics
  • Wnt Proteins / immunology


  • Osteoprotegerin
  • Tnfrsf11b protein, mouse
  • Tnfsf14 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Wnt Proteins
  • Wnt10b protein, mouse