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  • 标题:Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand
  • 本地全文:下载
  • 作者:Jau-Yi Li ; Hesham Tawfeek ; Brahmchetna Bedi
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2011
  • 卷号:108
  • 期号:2
  • 页码:768-773
  • DOI:10.1073/pnas.1013492108
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:estrogen ; osteoporosis
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