Bone diseases are increasing with aging populations and it is important to identify clues to develop innovative treatments. Vasn, which encodes vasorin (Vasn), a transmembrane protein involved in the pathophysiology of several organs, is expressed during the development in intramembranous and endochondral ossification zones. Here, we studied the impact of Vasn deletion on the osteoblast and osteoclast dialog through a cell Coculture model. In addition, we explored the bone phenotype of Vasn KO mice, either constitutive or tamoxifen‐inducible, or with an osteoclast‐specific deletion. First, we show that both osteoblasts and osteoclasts express Vasn. Second, we report that, in both KO mouse models but not in osteoclast‐targeted KO mice, Vasn deficiency was associated with an osteopenic bone phenotype, due to an imbalance in favor of osteoclastic resorption. Finally, through the Coculture experiments, we identify a dysregulation of the Wnt/β‐catenin pathway together with an increase in RANKL release by osteoblasts, which led to an enhanced osteoclast activity. This study unravels a direct role of Vasn in bone turnover, introducing a new biomarker or potential therapeutic target for bone pathologies.

中文翻译：

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瓦索林作为骨转换的演员？

随着人口老龄化，骨疾病不断增加，寻找线索来开发创新疗法非常重要。瓦森编码血管素 (Vasn)，这是一种参与多个器官病理生理学的跨膜蛋白，在膜内和软骨内骨化区的发育过程中表达。在这里，我们研究了瓦森通过细胞共培养模型删除成骨细胞和破骨细胞对话。此外，我们还探讨了骨表型瓦森KO 小鼠，无论是组成型小鼠还是他莫昔芬诱导型小鼠，或者具有破骨细胞特异性缺失的小鼠。首先，我们证明成骨细胞和破骨细胞都表达 Vasn。其次，我们报告说，在两种 KO 小鼠模型中，但不是在破骨细胞靶向 KO 小鼠中，瓦森由于有利于破骨细胞吸收的不平衡，缺乏与骨质减少的骨表型有关。最后，通过共培养实验，我们发现 Wnt/β-catenin 通路失调以及成骨细胞 RANKL 释放增加，从而导致破骨细胞活性增强。这项研究揭示了 Vasn 在骨转换中的直接作用，为骨病理学引入了新的生物标志物或潜在的治疗靶点。