Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
J Biol Chem. 2012 Aug 24;287(35):29851-60. doi: 10.1074/jbc.M112.377945. Epub 2012 Jul 10.
Production of the cytokine receptor activator of NFκB ligand (RANKL) by lymphocytes has been proposed as a mechanism by which sex steroid deficiency causes bone loss. However, there have been no studies that functionally link RANKL expression in lymphocytes with bone loss in this condition. Herein, we examined whether RANKL expression in either B or T lymphocytes contributes to ovariectomy-induced bone loss in mice. Mice harboring a conditional RANKL allele were crossed with CD19-Cre or Lck-Cre mice to delete RANKL in B or T lymphocytes, respectively. Deletion of RANKL from either cell type had no impact on bone mass in estrogen-replete mice up to 7 months of age. However, mice lacking RANKL in B lymphocytes were partially protected from the bone loss caused by ovariectomy. This protection occurred in cancellous, but not cortical, bone and was associated with a failure to increase osteoclast numbers in the conditional knock-out mice. Deletion of RANKL from T lymphocytes had no impact on ovariectomy-induced bone loss. These results demonstrate that lymphocyte RANKL is not involved in basal bone remodeling, but B cell RANKL does contribute to the increase in osteoclasts and cancellous bone loss that occurs after loss of estrogen.
细胞因子受体激活剂 NFκB 配体（RANKL）的产生被认为是性激素缺乏导致骨丢失的一种机制。然而，还没有研究从功能上将淋巴细胞中的 RANKL 表达与这种情况下的骨丢失联系起来。在此，我们研究了 B 或 T 淋巴细胞中 RANKL 的表达是否有助于小鼠去卵巢引起的骨丢失。携带条件性 RANKL 等位基因的小鼠与 CD19-Cre 或 Lck-Cre 小鼠杂交，分别在 B 或 T 淋巴细胞中删除 RANKL。在雌激素充足的情况下，直到 7 个月大，从任何一种细胞类型中删除 RANKL 都不会影响骨量。然而，B 淋巴细胞中缺乏 RANKL 的小鼠部分免受去卵巢引起的骨丢失的影响。这种保护作用发生在松质骨，而不是皮质骨，并且与条件敲除小鼠中破骨细胞数量的增加失败有关。T 淋巴细胞中 RANKL 的缺失对去卵巢引起的骨丢失没有影响。这些结果表明，淋巴细胞 RANKL 不参与基础骨重塑，但 B 细胞 RANKL 确实有助于雌激素丧失后破骨细胞和松质骨丢失的增加。
