期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 2, 页码 768-773出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1013492108
关键词
estrogen; osteoporosis
资金
- University of Alabama at Birmingham, Center for Metabolic Bone Disease-Histomorphometry Core Laboratory (National Institutes of Health) [P30-AR46031]
- National Institutes of Health [AR49659, AG28278]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR053607, AR059364]
- Veterans Affairs [5I01BX000105]
The bone loss induced by ovariectomy (ovx) has been linked to increased production of osteoclastogenic cytokines by bone marrow cells, including T cells and stromal cells (SCs). It is presently unknown whether regulatory interactions between these lineages contribute to the effects of ovx in bone, however. Here, we show that the T-cell costimulatory molecule CD40 ligand (CD40L) is required for ovx to expand SCs; promote osteoblast proliferation and differentiation; regulate the SC production of the osteoclastogenic factors macrophage colony-stimulating factor, receptor activator of nuclear factor-kappa B ligand, and osteoprotegerin; and up-regulate osteoclast formation. CD40L is also required for ovx to activate T cells and stimulate their production of TNF. Accordingly, ovx fails to promote bone loss and increase bone resorption in mice depleted of T cells or lacking CD40L. Therefore, cross-talk between T cells and SCs mediated by CD40L plays a pivotal role in the disregulation of osteoblastogenesis and osteoclastogenesis induced by ovx.
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