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 FAM20C mice to establish a Osx-Cre; FAM20C knockout (oKO) mouse model; FAM20C was KO in pre-osteoblasts. oKO development was examined at 1–10 weeks, in which compared to control FAM20C, 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.

中文翻译：

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敲除前成骨细胞中的 FAM20C 会导致破骨细胞分化上调，从而影响长骨发育

具有序列相似性的家族 20 成员 C (FAM20C) 是一种高尔基体酪蛋白激酶，可磷酸化参与骨发育和矿化的细胞外分泌调节蛋白，但其在骨发育中的具体作用仍很大程度上未知。在本研究中，为了探讨FAM20C影响骨骼发育的具体机制，我们将Osx-Cre与FAM20C小鼠杂交，建立了Osx-Cre； FAM20C敲除（oKO）小鼠模型； FAM20C 在前成骨细胞中被敲除。在 1-10 周时检查 oKO 发育，与对照 FAM20C 相比，它们的体重和骨组织矿化程度较低。此外，oKO 具有较低的骨体积分数、厚度和小梁数量，以及较高的小梁分离程度。这些小鼠的股骨干骺端软骨增殖层也减少，肥厚层增厚，凋亡细胞计数增加。转录组分析发现，oKO 中差异表达的基因集中在破骨细胞分化途径中，与破骨细胞存在的增加一致。此外，还发现破骨细胞相关基因上调，成骨相关基因下调，其中上调最多的基因是信号调节蛋白β-1家族（Sirpb1a-c）和丝裂原激活蛋白激酶13. 总体而言，前成骨细胞中的 FAM20C KO 会导致长骨发育异常，这可能是由于破骨细胞分化相关基因随后上调所致。