B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice.

Yan Li, Masakazu Terauchi, Tatyana Vikulina, Susanne Roser-Page, M N Weitzmann
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引用次数: 32

Abstract

Aging is a risk factor for osteoclastic bone loss and bone fracture. Receptor activator of NF-κB ligand (RANKL) is the key effector cytokine for osteoclastogenesis and bone resorption, and is moderated by its decoy receptor osteoprotegerin (OPG). The development of an inflammatory environment during aging leads to increased bone resorption and loss of bone mineral density (BMD). Interestingly, animal and clinical studies show that OPG is actually increased in aging but fails to fully compensate for endogenous RANKL. Osteoblast- and B-lineage cells are significant sources of physiological OPG, however osteoblast OPG production declines with age, suggesting that elevated OPG in aging may be a consequence of changes in B cell function. In this study we examined BMD and indices of trabecular bone structure during aging, and B cell production of both RANKL and OPG in young and aged mice. Our data reveal significant loss of BMD and trabecular structure with age commensurate with significantly elevated concentrations of both OPG and RANKL in aged mice, and a decline in B cell populations in aged animals. Taken together our data suggest that B cells may be responsible for the elevated concentrations of OPG during aging and are essential to counteract excessive age-associated bone resorption. Paradoxically, B cells themselves likely contribute RANKL in aging and the loss of B cells with age may further contribute to the imbalance in OPG relative to RANKL that predisposes age-associated bone loss.

Abstract Image

Abstract Image

Abstract Image

老年小鼠B细胞中OPG和RANKL的生成均显著增加。
衰老是破骨细胞骨质流失和骨折的危险因素。NF-κB配体受体激活因子(Receptor activator of NF-κB ligand, RANKL)是破骨细胞发生和骨吸收的关键效应细胞因子,受其诱骗受体骨保护素(osteoprotegerin, OPG)调控。衰老过程中炎症环境的发展导致骨吸收增加和骨矿物质密度(BMD)的损失。有趣的是,动物和临床研究表明,OPG实际上随着年龄的增长而增加,但不能完全补偿内源性RANKL。成骨细胞和B系细胞是生理性OPG的重要来源,然而成骨细胞OPG的产生随着年龄的增长而下降,这表明衰老过程中OPG的升高可能是B细胞功能变化的结果。在这项研究中,我们检测了衰老过程中幼龄和老年小鼠的骨密度和骨小梁结构指标,以及RANKL和OPG的B细胞生成。我们的数据显示,随着年龄的增长,老年小鼠的骨密度和小梁结构显著下降,OPG和RANKL浓度显著升高,老年动物的B细胞数量下降。综上所述,我们的数据表明,B细胞可能是导致衰老过程中OPG浓度升高的原因,并且对抵消与年龄相关的过度骨吸收至关重要。矛盾的是,B细胞本身可能在衰老过程中导致RANKL,随着年龄的增长,B细胞的丢失可能进一步导致OPG相对于RANKL的失衡,而RANKL易导致与年龄相关的骨质流失。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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