The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Medical College, Suzhou, Jiangsu, 215123, China.
CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.
Cell Death Dis. 2020 Dec 14;12(1):45. doi: 10.1038/s41419-020-03249-4.
Glucocorticoids (GC) are widely used clinically, despite the presence of significant side effects, including glucocorticoid-induced osteoporosis (GIOP). While GC are believed to act directly on osteoblasts and osteoclasts to promote osteoporosis, the detailed underlying molecular mechanism of GC-induced osteoporosis is still not fully elucidated. Here, we show that lymphocytes play a pivotal role in regulating GC-induced osteoporosis. We show that GIOP could not be induced in SCID mice that lack T cells, but it could be re-established by adoptive transfer of splenic T cells from wild-type mice. As expected, T cells in the periphery are greatly reduced by GC; instead, they accumulate in the bone marrow where they are protected from GC-induced apoptosis. These bone marrow T cells in GC-treated mice express high steady-state levels of NF-κB receptor activator ligand (RANKL), which promotes the formation and maturation of osteoclasts and induces osteoporosis. Taken together, these findings reveal a critical role for T cells in GIOP.
糖皮质激素（GC）在临床上被广泛应用，尽管存在明显的副作用，包括糖皮质激素诱导的骨质疏松症（GIOP）。虽然 GC 被认为可以直接作用于成骨细胞和破骨细胞来促进骨质疏松症，但 GC 诱导骨质疏松症的详细潜在分子机制仍未完全阐明。在这里，我们表明淋巴细胞在调节 GC 诱导的骨质疏松症中起着关键作用。我们表明，缺乏 T 细胞的 SCID 小鼠不能诱导 GIOP，但可以通过从野生型小鼠中过继转移脾 T 细胞来重新建立。正如预期的那样，GC 会大大减少外周血中的 T 细胞；相反，它们在骨髓中积累，在那里它们免受 GC 诱导的细胞凋亡的影响。GC 处理小鼠的骨髓 T 细胞表达高水平的 NF-κB 受体激活配体（RANKL），促进破骨细胞的形成和成熟，并诱导骨质疏松症。总之，这些发现揭示了 T 细胞在 GIOP 中的关键作用。
