破骨细胞
成骨细胞
生物
细胞生物学
内分泌学
内科学
遗传学
受体
医学
体外
作者
Lili Jiang,Xinpeng Liu,Lixue Liu,Lide Su,Zeyu Lu,Hong Zhao,Yuyao Guo,Wenxuan Zhang,Shujian Zhang,Wenxia Xu,Jiahui Zhang,Kai Zhang,Yuanbo Zhan,Xiaoyan Xie,R Li,Xiuzhu Dong,Jihong Han,Bin Zhang,Ying Liu
出处
期刊:Gene
[Elsevier]
日期:2024-07-01
卷期号:915: 148396-148396
标识
DOI:10.1016/j.gene.2024.148396
摘要
Family with sequence similarity 20 member C (FAM20C) is a Golgi casein kinase that phosphorylates extracellularly-secreted regulatory proteins involved in bone development and mineralization, but its specific role in bone development is still largely unknown. In this study, to examine the specific mechanisms that FAM20C influences bone development, we cross-bred Osx-Cre with FAM20Cflox/flox mice to establish a Osx-Cre; FAM20Cflox/flox knockout (oKO) mouse model; FAM20C was KO in pre-osteoblasts. oKO development was examined at 1–10 weeks, in which compared to control FAM20Cflox/flox, they had lower body weights and bone tissue mineralization. Furthermore, oKO had lower bone volume fractions, thickness, and trabecular numbers, along with higher degrees of trabecular separation. These mice also had decreased femoral metaphyseal cartilage proliferation layer, along with thickened hypertrophic layer and increased apoptotic cell counts. Transcriptomic analysis found that differentially-expressed genes in oKO were concentrated in the osteoclast differentiation pathway, in line with increased osteoclast presence. Additionally, up-regulation of osteoclast-related, and down-regulation of osteogenesis-related genes, were identified, in which the most up-regulated genes were signal regulatory protein β-1 family (Sirpb1a-c) and mitogen-activated protein kinase 13. Overall, FAM20C KO in pre-osteoblasts leads to abnormal long bone development, likely due to subsequent up-regulation of osteoclast differentiation-associated genes.
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