The critical role of T cells in glucocorticoid-induced osteoporosis

Lin Song, Lijuan Cao, Rui Liu, Hui Ma, Yanan Li, Qianwen Shang, Zhiyuan Zheng, Liying Zhang, Wen Zhang, Yuyi Han, Xiaoren Zhang, Huilin Yang, Ying Wang, Gerry Melino, Changshun Shao, Yufang Shi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Article number45
JournalCell Death and Disease
Volume12
Issue number1
DOIs
StatePublished - Jan 2021

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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