Prolyl hydroxylase domain proteins regulate bone mass through their expression in osteoblasts
Prolyl hydroxylase domain proteins regulate bone mass through their expression in osteoblasts
复制标题
脯氨酰羟化酶结构域蛋白通过在成骨细胞中的表达调节骨量
DOI：
10.1016/j.gene.2016.09.011
复制
发表时间：
2016
期刊：
影响因子：
3.5
通讯作者：
Xiao Guozhi
中科院分区：
文献类型：
--
作者：
Zhu Ke;Song Pingping;Lai Yumei;Liu Chuanju;Xiao Guozhi
脯氨酸羟基酶结构域蛋白(PhDS)在骨骼中的作用尚不完全清楚。在这里，我们通过用Col1a1-Cre转基因小鼠饲养FloxedPhd1-3小鼠，在小鼠的成骨细胞中删除了编码Phd1、PHD2和PHD3的基因的表达。结果表明，成骨细胞中缺乏Phd1-3(Phd1-3ob−/−)的小鼠骨量增加。与野生型(WT)相比，Phd1-3ob−/−的骨体积/组织体积(Bv/Tv)、骨小梁数量(Tb.N)和骨小梁厚度(Tb.Th)增加，而骨小梁间距(Tb.Sp)减小。相反，成骨细胞中PhD1-3的缺失并没有改变皮质厚度(Cort.Th)。与野生型(WT)骨相比，Phd1-3ob−/−骨的矿化聚集率(MAR)增加，表明成骨细胞功能增强。PhD1-3的缺失增加了骨髓培养中的成骨细胞前体细胞(CFU-OBS)的数量。有趣的是，删除成骨细胞中的Phd1-3基因会增加体外和骨骼中破骨细胞的形成。
The roles of prolyl hydroxylase domain proteins (PHDs) in bone are incompletely understood. Here we deleted the expression of genes encoding PHD1, PHD2, and PHD3 in osteoblasts in mice by breeding the floxedPhd1–3mice withCol1a1-Cretransgenic mice. Results showed that mice lacking PHD1-3 in osteoblasts (Phd1–3ob−/−) had increased bone mass. Bone parameters such as bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were increased, while trabecular spacing (Tb.Sp) was decreased inPhd1–3ob−/−relative to wild-type (WT) femurs. In contrast, loss of PHD1–3 in osteoblasts did not alter cortical thickness (Cort.Th). The mineralization apposition rate (MAR) was increased inPhd1–3ob−/−bone compared to that of wild-type (WT) bone, demonstrating an enhancement of osteoblast function. Loss of PHD1-3 increased the number of osteoblast progenitors (CFU-OBs) in bone marrow cultures. Interestingly, deletingPhd1–3genes in osteoblasts increased osteoclast formation in vitro and in bone.