The critical role of T cells in glucocorticoid-induced osteoporosis

• Published in: Cell death & disease 2020-12, Vol.12 (1), p.45-45, Article 45
• Main 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
• Format: Article
• Language: English
• Subjects: 13/31; 13/51; 14/19; 631/250/808; 631/80/304; 64/60; Adoptive transfer; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Bone marrow; Cell Biology; Cell Culture; Glucocorticoids; Immunology; Life Sciences; Lymphocytes; Lymphocytes T; NF-κB protein; Osteoblasts; Osteoclasts; Osteoporosis; Spleen; TRANCE protein
• ISSN: 2041-4889; 2041-4889
• 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.