纺神星
祖细胞
细胞生物学
成纤维细胞生长因子
间充质干细胞
兰克尔
成骨细胞
牙槽
癌症研究
骨重建
信号转导
骨愈合
炎症
医学
化学
生物
内分泌学
免疫学
内科学
干细胞
受体
解剖
牙科
肾
体外
激活剂(遗传学)
生物化学
作者
Yi Fan,Chen Cui,Clifford J. Rosen,Tadatoshi Sato,Ruoshi Xu,Peiran Li,Xi Wei,Ruiye Bi,Quan Yuan,Chenchen Zhou
标识
DOI:10.1038/s41392-022-00957-5
摘要
Maxillofacial bone defects are commonly seen in clinical practice. A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone regeneration. The fibroblast growth factor (FGF) signalling pathway is critical for the development of maxillofacial bone. Klotho, a type I transmembrane protein, is an important components of FGF receptor complexes. Recent studies have reported the presence of Klotho expression in bone. However, the role of Klotho in cranioskeletal development and repair remains unknown. Here, we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological conditions. Klotho-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in vivo. Under conditions of inflammation and trauma-induced bone loss, we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl expression. More importantly, we show for the first time that Klotho is present in human alveolar bone, with a distinct expression pattern under both normal and pathological conditions. In summary, our results identify the mechanism whereby Klotho expressed in Osx+-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and repair. Klotho-mediated signaling is an important component of alveolar bone remodeling and regeneration. It may also be a target for future therapeutics.
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