Bone loss induced by ovariectomy is due to the direct activity on bone cells and mesenchymal cells and to the dysregulated activity of bone marrow cells, including immune cells and stromal cells, but the underlying mechanisms are not completely known. Here, we demonstrate that ovariectomy induces the T‐cell co‐stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor‐κB ligand (RANKL). Predictably, LIGHT‐deficient (Tnfsf14^−/−) mice are protected from ovariectomy‐dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (Rag ^−/−Tnfsf14 ^−/−) and is associated with an inversion of the TNF and RANKL/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

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LIGHT / TNFSF14调节雌激素缺乏引起的骨质流失。

卵巢切除术引起的骨丢失是由于对骨细胞和间充质细胞的直接活性以及包括免疫细胞和基质细胞在内的骨髓细胞活性失调，但其潜在机制尚不完全清楚。在这里，我们证明卵巢切除术诱导T细胞共刺激细胞因子LIGHT，通过调节破骨细胞生成细胞因子的表达（包括TNF，骨保护素和核因子κB配体的受体激活剂）来刺激成骨细胞生成和破骨细胞生成。可以预见的是，缺乏光（Tnfsf14 ^-/-）的小鼠受到卵巢切除术依赖性骨丢失的保护，而缺乏光，T和B淋巴细胞的小鼠的小梁骨质量增加（Rag ^-/- Tnfsf14 ^-/-），并且与TNF和RANKL / OPG比值的倒置有关。此外，绝经后骨质疏松症的妇女在循环T细胞和单核细胞中显示出高水平的LIGHT。综上所述，这些结果表明LIGHT介导了卵巢切除术引起的骨质流失，这表明绝经后骨质疏松症患者可能会受益于LIGHT拮抗作用。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版