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- Title
The critical role of T cells in glucocorticoid-induced osteoporosis.
- Authors
Song, Lin; Cao, Lijuan; Liu, Rui; Ma, Hui; Li, Yanan; Shang, Qianwen; Zheng, Zhiyuan; Zhang, Liying; Zhang, Wen; Han, Yuyi; Zhang, Xiaoren; Yang, Huilin; Wang, Ying; Melino, Gerry; Shao, Changshun; Shi, Yufang
- Abstract
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.
- Publication
Cell Death & Disease, 2021, Vol 12, Issue 1, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-020-03249-4