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首页> 外文期刊>The FEBS journal >Subtilisin-like proprotein convertase paired basic amino acid-cleaving enzyme 4 is required for chondrogenic differentiation in ATDC5 cells
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Subtilisin-like proprotein convertase paired basic amino acid-cleaving enzyme 4 is required for chondrogenic differentiation in ATDC5 cells

机译：枯草杆菌蛋白酶样前蛋白转化酶配对的碱性氨基酸裂解酶4是ATDC5细胞软骨分化所需的

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摘要

Bone morphogenetic proteins (BMPs) have been implicated in the regulation of multiple stages of endochondral bone development. BMPs are synthesized as inactive precursors, and activated by removal of the propeptide. The subtilisin-like proprotein convertase (SPC) family comprises seven members [furin/SPC1, PC2/SPC2, PC1/PC3/SPC3, paired basic amino acid-cleaving enzyme 4 (PACE4)/SPC4, PC4/SPC5, PC6/PC5/SPC6, and PC8/PC7/LPC/SPC7], and activates various signaling molecules, including BMPs. In this study, we analyzed the role of this family in chondrogenic differentiation by using the mouse embryonal carcinoma-derived clonal cell line ATDC5. Both SPC-specic inhibitors, decanoyl-Arg-Val-Lys-Arg-chloromethylketone and a1-antitrypsin Portland variant, suppressed chondrogenic differentiation. RT-PCR analysis revealed that PACE4 mRNA levels increased markedly during chondrogenic differentiation, whereas furin expression remained unchanged. Knockdown of PACE4 expression signi- cantly reduced chondrogenic differentiation. Furthermore, proBMP6, which shows an expression pattern similar to that of PACE4, was efciently processed into its mature form by PACE4, whereas furin could not process proBMP6. These results suggest that PACE4 may regulate the rate of hypertrophic conversion of ATDC5 cells through activation of proBMP6.
机译：骨形态发生蛋白（BMP）已牵涉到软骨内骨发育的多个阶段的调节。 BMP被合成为无活性的前体，并通过去除前肽而被激活。枯草杆菌蛋白酶样前蛋白转化酶（SPC）家族包含七个成员[弗林蛋白酶/ SPC1，PC2 / SPC2，PC1 / PC3 / SPC3，成对的碱性氨基酸裂解酶4（PACE4）/ SPC4，PC4 / SPC5，PC6 / PC5 / SPC6和PC8 / PC7 / LPC / SPC7]，并激活各种信号分子，包括BMP。在这项研究中，我们通过使用小鼠胚胎癌衍生的克隆细胞系ATDC5分析了该家族在软骨分化中的作用。两种SPC特异性抑制剂癸酰基-Arg-Val-Lys-Arg-氯甲基酮和a1-抗胰蛋白酶波特兰变体均抑制软骨形成分化。 RT-PCR分析表明，软骨形成分化过程中PACE4 mRNA水平显着增加，而弗林蛋白酶的表达保持不变。抑制PACE4表达可显着降低软骨形成分化。此外，显示出类似于PACE4的表达模式的proBMP6被PACE4有效地加工成其成熟形式，而弗林蛋白酶则不能加工proBMP6。这些结果表明，PACE4可能通过激活proBMP6来调节ATDC5细胞的肥大转化率。

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