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 CD8þ T cells in Tnfsf14-/-mice. LIGHT stimulation increases OPG levels in B, CD8þ T, and osteoblastic cells, as well as Wnt10b expression in CD8þ 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.

Impairment of Bone Remodeling in LIGHT/TNFSF14-Deficient Mice / Brunetti, Giacomina; Felicia Faienza, Maria; Colaianni, Graziana; Gigante, Isabella; Oranger, Angela; Pignataro, Paolo; Ingravallo, Giuseppe; Di Benedetto, Adriana; Bortolotti, Sara; Di Comite, Mariasevera; Storlino, Giuseppina; Lippo, Luciana; Ward-Kavanagh, Lindsay; Mori, Giorgio; Reseland, Janne E.; Passeri, Giovanni; Schipani, Ernestina; Tamada, Koji; Ware, Carl F.; Colucci, Silvia; Maria Grano, And. - In: JOURNAL OF BONE AND MINERAL RESEARCH. - ISSN 1523-4681. - 33:4(2018), pp. 704-719. [10.1002/jbmr.3345]

Impairment of Bone Remodeling in LIGHT/TNFSF14-Deficient Mice

Giovanni Passeri;
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 CD8þ T cells in Tnfsf14-/-mice. LIGHT stimulation increases OPG levels in B, CD8þ T, and osteoblastic cells, as well as Wnt10b expression in CD8þ 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.
Impairment of Bone Remodeling in LIGHT/TNFSF14-Deficient Mice / Brunetti, Giacomina; Felicia Faienza, Maria; Colaianni, Graziana; Gigante, Isabella; Oranger, Angela; Pignataro, Paolo; Ingravallo, Giuseppe; Di Benedetto, Adriana; Bortolotti, Sara; Di Comite, Mariasevera; Storlino, Giuseppina; Lippo, Luciana; Ward-Kavanagh, Lindsay; Mori, Giorgio; Reseland, Janne E.; Passeri, Giovanni; Schipani, Ernestina; Tamada, Koji; Ware, Carl F.; Colucci, Silvia; Maria Grano, And. - In: JOURNAL OF BONE AND MINERAL RESEARCH. - ISSN 1523-4681. - 33:4(2018), pp. 704-719. [10.1002/jbmr.3345]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2836438
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