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,可磷酸化参与骨骼发育和矿化的细胞外分泌调节蛋白,但其在骨骼发育中的具体作用尚不清楚。在这项研究中,为了检查FAM20C影响骨骼发育的具体机制,我们将Osx-Cre与FAM20Cflox/flox小鼠杂交,建立Osx-Cre;FAM20Cflox/flox基因敲除(oKO)小鼠模型;FAM20C是前成骨细胞中的KO。在1-10周检查oKO发育,其中与对照FAM20Cflox/flox相比,他们的体重较低,骨组织矿化。此外,OKO的骨体积分数较低,厚度,和骨小梁数量,伴随着更高程度的小梁分离。这些小鼠的股骨干端软骨增生层也减少,随着肥厚层增厚和凋亡细胞计数增加。转录组学分析发现,OKO中差异表达的基因集中在破骨细胞分化途径,与破骨细胞的存在增加一致。此外,与破骨细胞相关的上调,和下调成骨相关基因,被确认,其中上调最多的基因是信号调节蛋白β-1家族(Sirpb1a-c)和丝裂原活化蛋白激酶13。总的来说,前成骨细胞中的FAM20CKO导致长骨发育异常,可能是由于随后的破骨细胞分化相关基因的上调。
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.