Postnatal deletion of β-catenin in osterix-expressing cells is necessary for bone growth and intermittent PTH-induced bone gain.
Postnatal deletion of β-catenin in osterix-expressing cells is necessary for bone growth and intermittent PTH-induced bone gain.
复制标题
出生后 osterix 表达细胞中β-连环蛋白的缺失对于骨骼生长和间歇性 PTH 诱导的骨增益是必要的。
DOI：
10.1007/s00774-017-0873-0
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Lige Song
中科院分区：
文献类型：
--
作者：
Caixia Yu;Miao Xuan;Mingzhu Zhang;Lige Song
wnt/β-连环蛋白信号传导已显示影响骨稳态，并且对于甲状旁腺激素（PTH）诱导的骨获得是重要的。为了进一步了解β-连环蛋白在成骨细胞谱系细胞早期阶段对出生后骨稳态的作用以及PTH对骨的合成代谢作用，我们通过将floxed β-连环蛋白小鼠与表达cre的转基因小鼠交配，检测了在多西环素可抑制的osterix启动子控制下，osterix表达细胞中β-连环蛋白出生后破坏的小鼠（β-连环蛋白KO小鼠）。停用强力霉素后，β-连环蛋白基因敲除小鼠出现进行性骨丢失、异位软骨形成、间充质基质细胞积聚和骨髓肥胖。通过流式细胞术从β-连环蛋白KO小鼠中分选的β-连环蛋白缺陷型成骨细胞表现出EdU掺入减少、膜联蛋白V活性增加以及基因表达的显著改变，包括wnt靶基因、破骨细胞调节因子和成骨细胞标志物。在新生儿和出生后的β-连环蛋白KO小鼠中观察到破骨细胞的急剧增加。间歇给予PTH 4周显著增加对照小鼠的骨量;然而，PTH的这种合成代谢作用在β-连环蛋白KO小鼠中基本上减弱。我们的数据表明，osterix表达细胞中的β-连环蛋白是出生后成骨细胞分化、成骨细胞增殖和骨吸收所必需的，并且是骨中PTH合成代谢作用所必需的。
wnt/β-catenin signaling has been shown to influence bone homeostasis and is important for parathyroid hormone (PTH)-induced bone gain. To further understand the role of β-catenin in the early stages of osteoblastic lineage cells for postnatal bone homeostasis and the anabolic actions of PTH on bone, we examined mice with postnatal disruption of β-catenin in osterix-expressing cells (β-catenin KO mice) by mating floxed β-catenin mice with transgenic mice expressing cre under the control of the osterix promoter suppressible by doxycycline. After withdrawal of doxycycline, β-catenin KO mice developed progressive bone loss, ectopic cartilage formation, accumulation of mesenchymal stromal cells, and bone marrow adiposity. The β-catenin-defective osteoblasts sorted by flow cytometry from β-catenin KO mice exhibited decreased EdU incorporation, increased annexin V activity, and profound alterations in gene expression including wnt target genes, osteoclast regulators, and osteoblast markers. A dramatic increase in osteoclasts was observed in both neonatal and postnatal β-catenin KO mice. Intermittent administration of PTH for 4 weeks significantly increased bone mass in control mice; however, this anabolic effect of PTH was substantially blunted in β-catenin KO mice. Our data indicate that β-catenin in osterix-expressing cells is required for postnatal osteoblast differentiation, osteoblast proliferation, and bone resorption, and is essential for the anabolic actions of PTH in bone.