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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 >β-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice
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β-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice

机译：β-catenin促进出生后生长小鼠的骨形成并抑制骨吸收

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Genetic studies in the mouse have demonstrated multiple roles for β-catenin in the skeleton. In the embryo, β-catenin is critical for the early stages of osteoblast differentiation. Postnatally, β-catenin in mature osteoblasts and osteocytes indirectly suppresses osteoclast differentiation. However, a direct role for β-catenin in regulating osteoblast number and/or function specifically in the postnatal life has not been demonstrated. Addressing this knowledge gap is important because low-density lipoprotein receptor-related protein 5 (LRP5), a coreceptor for WNT signaling proposed to function through β-catenin, controls osteoblast number and function in postnatal mice or humans. To overcome the neonatal lethality caused by embryonic deletion of β-catenin in early-stage osteoblast-lineage cells, we use the Osx-CreERT2 mouse strain to remove β-catenin in Osterix (Osx)-expressing cells by administering tamoxifen (TM) temporarily to postnatal mice. Lineage-tracing experiments in the long bones demonstrate that Osx-CreERT2 targets predominantly osteoblast-lineage cells on the bone surface, but also transient progenitors that contribute to bone marrow stromal cells and adipocytes. Deletion of β-catenin by this strategy greatly reduces the bone formation activity of the targeted osteoblasts. However, the targeted osteoblasts rapidly turn over and are replaced by an excessive number of non-targeted osteoblasts, causing an unexpected increase in bone formation, but an even greater increase in osteoclast number and activity produces a net effect of severe osteopenia. With time, the mutant mice also exhibit a marked increase in bone marrow adiposity. Thus, β-catenin in postnatal Osx-lineage cells critically regulates bone homeostasis by promoting osteoblast activity and suppressing osteoblast turnover, while restraining osteoclast and marrow fat formation.
机译：小鼠的遗传研究表明，β-连环蛋白在骨骼中具有多种作用。在胚胎中，β-catenin对成骨细胞分化的早期至关重要。出生后，成熟成骨细胞和骨细胞中的β-catenin间接抑制破骨细胞分化。然而，尚未证明β-连环蛋白在调节成骨细胞数量和/或特别是在产后生活中的直接作用。解决这一知识空白非常重要，因为低密度脂蛋白受体相关蛋白5（LRP5）是WNT信号转导的核心受体，被提议通过β-catenin发挥功能，控制成骨小鼠或人类的成骨细胞数量和功能。为了克服早期成骨细胞系细胞中β-catenin胚胎缺失引起的新生儿致死性，我们使用Osx-CreERT2小鼠品系通过临时施用他莫昔芬（TM）去除表达Osterix（Osx）的细胞中的β-catenin。产后小鼠。长骨的谱系追踪实验表明，Osx-CreERT2主要靶向骨表面的成骨细胞谱系细胞，但也靶向促成骨髓基质细胞和脂肪细胞的瞬时祖细胞。通过这种策略删除β-catenin会大大降低目标成骨细胞的骨形成活性。然而，靶向成骨细胞迅速翻身，并被过量的非靶向成骨细胞所替代，从而导致骨形成的意外增加，但是破骨细胞数量和活性的更大提高产生了严重的骨质减少的净效应。随着时间的推移，突变小鼠的骨髓脂肪也显着增加。因此，产后Osx系细胞中的β-catenin可通过促进成骨细胞活性和抑制成骨细胞更新，同时抑制破骨细胞和骨髓脂肪的形成来关键地调节骨稳态。

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