首页> 美国卫生研究院文献>Scientific Reports >The osteoprogenitor-specific loss of ephrinB1 results in an osteoporotic phenotype affecting the balance between bone formation and resorption
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The osteoprogenitor-specific loss of ephrinB1 results in an osteoporotic phenotype affecting the balance between bone formation and resorption

机译:ephrinB1的骨祖细胞特异性丢失导致骨质疏松表型影响骨形成和吸收之间的平衡

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摘要

The present study investigated the effects of conditional deletion of ephrinB1 in osteoprogenitor cells driven by the Osterix (Osx) promoter, on skeletal integrity in a murine model of ovariectomy-induced (OVX) osteoporosis. Histomorphometric and μCT analyses revealed that loss of ephrinB1 in sham Osx:cre-ephrinB1fl/fl mice caused a reduction in trabecular bone comparable to OVX Osx:Cre mice, which was associated with a significant reduction in bone formation rates and decrease in osteoblast numbers. Interestingly, these observations were not exacerbated in OVX Osx:cre-ephrinB1fl/fl mice. Furthermore, sham Osx:cre-ephrinB1fl/fl mice displayed significantly higher osteoclast numbers and circulating degraded collagen type 1 compared to OVX Osx:Cre mice. Confirmation studies found that cultured monocytes expressing EphB2 formed fewer TRAP+ multinucleated osteoclasts and exhibited lower resorption activity in the presence of soluble ephrinB1-Fc compared to IgG control. This inhibition of osteoclast formation and function induced by ephrinB1-Fc was reversed in the presence of an EphB2 chemical inhibitor. Collectively, these observations suggest that ephrinB1, expressed by osteoprogenitors, influences bone loss during the development of osteoporosis, by regulating both osteoblast and osteoclast formation and function, leading to a loss of skeletal integrity.
机译:本研究调查了卵巢切除术诱发的骨质疏松症小鼠模型中由Osterix(Osx)启动子驱动的骨祖细胞中有条件缺失ephrinB1对骨骼完整性的影响。组织形态计量学和μCT分析表明,与OVX Osx:Cre小鼠相比,假Osx:cre-ephrinB1 fl / fl 小鼠中的ephrinB1丢失导致小梁骨减少,这与骨骼的显着减少有关形成率和成骨细胞数量减少。有趣的是,这些观察结果在OVX Osx:cre-ephrinB1 fl / fl 小鼠中并未加剧。此外,与OVX Osx:Cre小鼠相比,假Osx:cre-ephrinB1 fl / fl 小鼠显示出明显更高的破骨细胞数量和1型循环降解胶原蛋白。确认研究发现,与IgG对照相比,培养的表达EphB2的单核细胞形成更少的TRAP + 多核破骨细胞,并且在可溶性ephrinB1-Fc存在下表现出较低的吸收活性。在EphB2化学抑制剂的存在下,这种由ephrinB1-Fc诱导的破骨细胞形成和功能的抑制作用被逆转。总体而言,这些观察结果表明,由骨祖细胞表达的ephrinB1通过调节成骨细胞和破骨细胞的形成和功能来影响骨质疏松发展过程中的骨质流失,从而导致骨骼完整性的丧失。

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