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Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment
Bone Research ( IF 14.3 ) Pub Date : 2022-01-27 , DOI: 10.1038/s41413-021-00172-y
Anke Baranowsky 1, 2 , Denise Jahn 3, 4 , Shan Jiang 1 , Timur Yorgan 2 , Peter Ludewig 5 , Jessika Appelt 3, 4 , Kai K Albrecht 4 , Ellen Otto 3, 4 , Paul Knapstein 1 , Antonia Donat 1 , Jack Winneberger 5 , Lana Rosenthal 2 , Paul Köhli 3, 4 , Cordula Erdmann 1 , Melanie Fuchs 3, 4 , Karl-Heinz Frosch 1 , Serafeim Tsitsilonis 3, 4 , Michael Amling 2 , Thorsten Schinke 2 , Johannes Keller 1, 6
Affiliation  

Intermittent injections of parathyroid hormone (iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone (PTH) primarily results in increased bone resorption. Here, we identified Calca, encoding the sepsis biomarker procalcitonin (ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.



中文翻译:

降钙素原在成骨细胞中表达,并通过在间歇性 PTH 治疗期间抑制巨噬细胞迁移来限制骨吸收

间歇性注射甲状旁腺激素 (iPTH) 在临床上用于刺激成骨细胞形成骨,尽管甲状旁腺激素 (PTH) 的持续升高主要导致骨吸收增加。在这里,我们确定了Calca,编码脓毒症生物标志物降钙素原 (ProCT),作为抑制破骨细胞形成的小鼠成骨细胞中 PTH 的新靶基因。在 iPTH 治疗期间,缺乏 ProCT 的小鼠的骨吸收增加,长骨和轴向骨骼中破骨细胞形成过多。从机制上讲,ProCT 抑制参与巨噬细胞募集的关键介质的表达,这些介质代表破骨细胞前体。因此,ProCT 阻止巨噬细胞迁移并导致早期但不是晚期破骨细胞生成的抑制。总之,我们的结果揭示了成骨细胞衍生的 ProCT 在骨微环境中的潜在作用,这是限制 iPTH 期间骨吸收所必需的。

更新日期:2022-01-30
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