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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice.
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DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice.

机译：DLK1是一种新型的骨量调节剂，可介导雌激素缺乏引起的小鼠骨质流失。

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Delta-like 1/fetal antigen 1 (DLK1/FA-1) is a transmembrane protein belonging to the Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific Dlk1-overexpressing mice (Col1-Dlk1). Col1-Dlk1 mice displayed growth retardation and significantly reduced total body weight and bone mineral density (BMD). Micro-computed tomographis (microCT) scanning revealed a reduced trabecular and cortical bone volume fraction. Tissue-level histomorphometric analysis demonstrated decreased bone-formation rate and enhanced bone resorption in Col1-Dlk1 mice compared with wild-type mice. At a cellular level, Dlk1 markedly reduced the total number of bone marrow (BM)-derived colony-forming units fibroblasts (CFU-Fs), as well as their osteogenic capacity. In a number of in vitro culture systems, Dlk1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of proinflammatory bone-resorbing cytokines (eg, Il7, Tnfa, and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of Dlk1 in the bone marrow by activated T cells. Interestingly, Dlk1(-/-) mice were significantly protected from ovx-induced bone loss compared with wild-type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1 production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss.
机译：三角洲样1 /胎儿抗原1（DLK1 / FA-1）是属于Notch / Delta家族的跨膜蛋白，可作为膜相关蛋白或可溶性蛋白来调节许多成年组织的再生。在这里，我们使用成骨细胞特异性Dlk1过表达小鼠（Col1-Dlk1）检查了DLK1 / FA-1在骨骼生物学中的作用。 Col1-Dlk1小鼠表现出生长迟缓，并显着降低了总体重和骨矿物质密度（BMD）。微型计算机断层扫描（microCT）扫描显示小梁和皮质骨体积分数降低。组织水平的组织形态分析表明，与野生型小鼠相比，Col1-Dlk1小鼠的骨形成速率降低且骨吸收增强。在细胞水平上，Dlk1显着减少了源自骨髓（BM）的集落形成单位成纤维细胞（CFU-Fs）的总数及其成骨能力。在许多体外培养系统中，Dlk1通过成骨细胞依赖性促炎性骨吸收细胞因子（例如，Il7，Tnfa和Ccl3）的产生增加而间接刺激破骨细胞生成。我们发现卵巢切除术（ovx）诱导的骨丢失与活化T细胞在骨髓中Dlk1的产生增加有关。有趣的是，与野生型小鼠相比，Dlk1（-/-）小鼠受到了ovx诱导的骨丢失的显着保护。因此，我们确定Dlk1是一种新型的骨量调节剂，其功能是抑制骨形成并刺激骨吸收。在雌激素缺乏的情况下，T细胞产生的DLK1产量增加，表明其可能用作预防绝经后骨质流失的治疗靶标。

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