Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand
Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand
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DOI：
10.1073/pnas.1013492108
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发表时间：
2011-01-11
影响因子：
11.1
通讯作者：
Pacifici, Roberto
中科院分区：
文献类型：
--
作者：
Li, Jau-Yi;Tawfeek, Hesham;Pacifici, Roberto
卵巢切除术（ovx）引起的骨质流失与骨髓细胞（包括T细胞和基质细胞（SCs））产生的破骨细胞因子增加有关。然而，目前尚不清楚这些谱系之间的调节相互作用是否有助于ovx在骨中的作用。在这里，我们发现t细胞共刺激分子CD40配体（CD40L）是ovx扩增SCs所必需的；促进成骨细胞增殖和分化；调节SC生成破骨细胞因子巨噬细胞集落刺激因子、核因子κ B配体受体激活因子和骨保护素；上调破骨细胞的形成。ovx也需要CD40L来激活T细胞并刺激它们产生TNF。因此，在T细胞缺失或CD40L缺失的小鼠中，ovx不能促进骨质流失和增加骨吸收。因此，CD40L介导的T细胞与SCs间的串扰在ovx诱导的成骨细胞生成和破骨细胞生成的失调中起着关键作用。
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.