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.

Impairment of Bone Remodeling in LIGHT/TNFSF14-Deficient Mice

Di Benedetto, Adriana;Mori, Giorgio;Grano, Maria
2018

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11369/368611
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