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, G., Felicia Faienza, M., Colaianni, G., Gigante, I., Oranger, A., Pignataro, P., Ingravallo, G., Di Benedetto, A., Bortolotti, S., Di Comite, M., Storlino, G., Lippo, L., Ward-Kavanagh, L., Mori, G., Reseland, J.E., Passeri, G., Schipani, E., Tamada, K., Ware, C.F., Colucci, S., et al.. - 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;
2018-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
