Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Bari, Italy.
Department of Biomedical Science and Human Oncology, Paediatric Unit, University of Bari, Bari, Italy.
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.
多种免疫细胞产生的细胞因子通过成骨细胞（osteoblasts）和破骨细胞（osteoclasts）的分化诱导重塑，并有助于维持骨内稳态。在这里，我们研究了肿瘤坏死因子（TNF）超家族细胞因子 LIGHT 控制的骨重塑。与 WT 小鼠相比，LIGHT 缺陷型小鼠（Tnfsf14）表现出脊柱畸形和股骨松质骨量减少，其与破骨细胞数量增加和成骨细胞数量略有减少有关。LIGHT 在骨细胞中的作用可以是直接的，也可以是间接的，既可以通过 B 和 T 细胞中抗破骨细胞生成的骨保护素（osteoprotegerin，OPG）表达降低以及 CD8 T 细胞中促成骨细胞生成的 Wnt10b 水平降低来介导，也可以通过这种方式来介导。LIGHT 刺激可增加 B、CD8 T 和成骨细胞中的 OPG 水平，以及 CD8 T 细胞中的 Wnt10b 表达。Light 和 T、B 细胞缺陷型小鼠（Rag /Tnfsf14）中的高骨量支持免疫系统在骨内稳态中的协同作用。这些结果表明 LIGHT 可能是骨疾病的一个潜在靶点。
