Fujiwara Yuko, Piemontese Marilina, Liu Yu, Thostenson Jeff D, Xiong Jinhu, O'Brien Charles A
From the Center for Osteoporosis and Metabolic Bone Diseases and.
Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205.
J Biol Chem. 2016 Nov 25;291(48):24838-24850. doi: 10.1074/jbc.M116.742452. Epub 2016 Oct 12.
The cytokine receptor activator of NFκB ligand (RANKL) produced by osteocytes is essential for osteoclast formation in cancellous bone under physiological conditions, and RANKL production by B lymphocytes is required for the bone loss caused by estrogen deficiency. Here, we examined whether RANKL produced by osteocytes is also required for the bone loss caused by estrogen deficiency. Mice lacking RANKL in osteocytes were protected from the increase in osteoclast number and the bone loss caused by ovariectomy. Moreover, these mice did not exhibit the increase in bone marrow B lymphocytes caused by ovariectomy that occurred in control littermates. Deletion of estrogen receptor α from B cells did not alter B cell number or bone mass and did not alter the response to ovariectomy. In addition, lineage-tracing studies demonstrated that B cells do not act as osteoclast progenitors in estrogen-replete or estrogen-deficient mice. Taken together, these results demonstrate that RANKL expressed by osteocytes is required for the bone loss as well as the increase in B cell number caused by estrogen deficiency. Moreover, they suggest that estrogen control of B cell number is indirect via osteocytes and that the increase in bone marrow B cells may be a necessary component of the cascade of events that lead to cancellous bone loss during estrogen deficiency. However, the role of B cells is not to act as osteoclast progenitors but may be to act as osteoclast support cells.
在生理条件下，骨细胞产生的核因子κB受体激活蛋白配体（RANKL）对于松质骨中破骨细胞的形成至关重要，而雌激素缺乏导致的骨质流失需要B淋巴细胞产生RANKL。在此，我们研究了骨细胞产生的RANKL对于雌激素缺乏导致的骨质流失是否也是必需的。骨细胞中缺乏RANKL的小鼠可免受破骨细胞数量增加以及卵巢切除引起的骨质流失的影响。此外，这些小鼠并未表现出卵巢切除引起的骨髓B淋巴细胞增加，而对照同窝小鼠则出现了这种情况。从B细胞中删除雌激素受体α并未改变B细胞数量或骨量，也未改变对卵巢切除的反应。此外，谱系追踪研究表明，在雌激素充足或缺乏的小鼠中，B细胞并非破骨细胞祖细胞。综上所述，这些结果表明，骨细胞表达的RANKL对于雌激素缺乏导致的骨质流失以及B细胞数量增加是必需的。此外，它们表明雌激素对B细胞数量的控制是通过骨细胞间接实现的，并且骨髓B细胞的增加可能是雌激素缺乏期间导致松质骨流失的一系列事件中的必要组成部分。然而，B细胞的作用不是作为破骨细胞祖细胞，而是可能作为破骨细胞支持细胞。
