Crucial Role of Elovl6 in Chondrocyte Growth and Differentiation during Growth Plate Development in Mice.
Crucial Role of Elovl6 in Chondrocyte Growth and Differentiation during Growth Plate Development in Mice.
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DOI：
10.1371/journal.pone.0159375
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Shimano H
中科院分区：
文献类型：
--
作者：
Kikuchi M;Shimada M;Matsuzaka T;Ishii K;Nakagawa Y;Takayanagi M;Yamada N;Shimano H
极长链脂肪酸的延长（Elov 16）是一种微粒体酶，其调节C12-16饱和和单不饱和脂肪酸的延长。Elov 16已显示与各种病理生理学相关，包括胰岛素抗性、动脉粥样硬化和非酒精性脂肪性肝炎。为了研究Elov 16在骨发育过程中的潜在作用，我们在此检查了Elov 16敲除（Elov 16-/-）小鼠的骨骼表型。Elov 16-/-骨架比对照小，但没有表现出明显的图案化缺陷。组织学分析显示，与对照组相比，Elov 16-/-小鼠增殖长度减少，肥大软骨细胞层长度延长，骨小梁减少。这些结果可能是由于软骨细胞增殖的适度减少和软骨细胞谱系细胞的加速分化。与Elov 16-/-小鼠中肥大软骨细胞层长度增加一致，胶原10 α1被鉴定为软骨细胞中Elov 16消融最受影响的基因之一。此外，Elov 16缺失的软骨细胞的胶原10 α1的这种升高的表达可能与Foxa 2/a3和Mef 2c mRNA表达水平的增加相关。在软骨细胞谱系的Elov 16敲低细胞中也观察到核Foxa 2和细胞质组蛋白脱乙酰化酶4/5/7的蛋白水平的相对增加。总的来说，我们的数据表明Elovl 6对胚胎生长板的正常发育起着关键作用。
ELOVL family member 6, elongation of very long chain fatty acids (Elovl6) is a microsomal enzyme, which regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 has been shown to be associated with various pathophysiologies including insulin resistance, atherosclerosis, and non-alcoholic steatohepatitis. To investigate a potential role of Elovl6 during bone development, we here examined a skeletal phenotype of Elovl6 knockout (Elovl6-/-) mice. The Elovl6-/- skeleton was smaller than that of controls, but exhibited no obvious patterning defects. Histological analysis revealed a reduced length of proliferating and an elongated length of hypertrophic chondrocyte layer, and decreased trabecular bone in Elovl6-/- mice compared with controls. These results were presumably due to a modest decrease in chondrocyte proliferation and accelerated differentiation of cells of the chondrocyte lineage. Consistent with the increased length of the hypertrophic chondrocyte layer in Elovl6-/- mice, Collagen10α1 was identified as one of the most affected genes by ablation of Elovl6 in chondrocytes. Furthermore, this elevated expression of Collagen10α1 of Elovl6-null chondrocytes was likely associated with increased levels of Foxa2/a3 and Mef2c mRNA expression. Relative increases in protein levels of nuclear Foxa2 and cytoplasmic histone deacethylase 4/5/7 were also observed in Elovl6 knockdown cells of the chondrocyte lineage. Collectively, our data suggest that Elovl6 plays a critical role for proper development of embryonic growth plate.