The critical role of T cells in glucocorticoid-induced osteoporosis

Cell Death Dis. 2020 Dec 14;12(1):45. doi: 10.1038/s41419-020-03249-4.

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Chemokines / immunology
  • Dexamethasone / adverse effects
  • Dexamethasone / pharmacology
  • Female
  • Femur / drug effects
  • Femur / pathology
  • Glucocorticoids / adverse effects*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, SCID
  • Osteoporosis / chemically induced*
  • Osteoporosis / immunology*
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • RANK Ligand / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Chemokines
  • Glucocorticoids
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Dexamethasone