Receptor Activator of Nuclear Factor κB Ligand (RANKL) Protein Expression by B Lymphocytes Contributes to Ovariectomy-induced Bone Loss
Receptor Activator of Nuclear Factor κB Ligand (RANKL) Protein Expression by B Lymphocytes Contributes to Ovariectomy-induced Bone Loss
复制标题
DOI：
10.1074/jbc.m112.377945
复制
发表时间：
2012-08-24
影响因子：
4.8
通讯作者：
O'Brien, Charles A.
中科院分区：
文献类型：
--
作者：
Onal, Melda;Xiong, Jinhu;O'Brien, Charles A.
淋巴细胞产生NF kappa B配体细胞因子受体激活剂（RANKL）已被认为是性类固醇缺乏导致骨质流失的一种机制。然而，还没有研究表明淋巴细胞中RANKL表达与这种情况下的骨丢失在功能上相关。在此，我们检查了B或T淋巴细胞中RANKL的表达是否有助于卵巢切除术诱导的小鼠骨丢失。携带条件性RANKL等位基因的小鼠与CD 19-Cre或Lck-Cre小鼠杂交，以分别删除B或T淋巴细胞中的RANKL。从任一细胞类型中删除RANKL对7月龄内雌激素充足小鼠的骨量没有影响。然而，B淋巴细胞中缺乏RANKL的小鼠可以部分免受卵巢切除术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，并且与条件性基因敲除小鼠中破骨细胞数量增加失败有关。T淋巴细胞中RANKL的缺失对卵巢切除术诱导的骨丢失没有影响。这些结果表明，淋巴细胞RANKL不参与基底骨重塑，但B细胞RANKL确实有助于雌激素丢失后发生的破骨细胞和松质骨丢失的增加。
Production of the cytokine receptor activator of NF kappa B 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.