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Subtilisin‐like proprotein convertase paired basic amino acid‐cleaving enzyme 4 is required for chondrogenic differentiation in ATDC 5 cells
Author(s) -
Yuasa Keizo,
Futamatsu Go,
Kawano Tsuyoshi,
Muroshita Masaki,
Kageyama Yoko,
Taichi Hiromi,
Ishikawa Hiroshi,
Nagahama Masami,
Matsuda Yoshiko,
Tsuji Akihiko
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2012.08758.x
Subject(s) - furin , proprotein convertases , chondrogenesis , subtilisin , proprotein convertase , microbiology and biotechnology , gene knockdown , biochemistry , endochondral ossification , biology , chemistry , enzyme , cartilage , cell , gene , anatomy , lipoprotein , ldl receptor , cholesterol
Bone morphogenetic proteins ( BMP s) have been implicated in the regulation of multiple stages of endochondral bone development. BMP s are synthesized as inactive precursors, and activated by removal of the propeptide. The subtilisin‐like proprotein convertase ( SPC ) family comprises seven members [furin/ SPC 1, PC 2/ SPC 2, PC 1/ PC 3/ SPC 3, paired basic amino acid‐cleaving enzyme 4 ( PACE 4)/ SPC 4, PC 4/ SPC 5, PC 6/ PC 5/ SPC 6, and PC 8/ PC 7/ LPC / SPC 7], and activates various signaling molecules, including BMP s. In this study, we analyzed the role of this family in chondrogenic differentiation by using the mouse embryonal carcinoma‐derived clonal cell line ATDC 5. Both SPC ‐specific inhibitors, decanoyl‐ A rg‐ V al‐ L ys‐ A rg‐chloromethylketone and α1‐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 PACE 4 expression significantly reduced chondrogenic differentiation. Furthermore, proBMP6, which shows an expression pattern similar to that of PACE 4, was efficiently processed into its mature form by PACE 4, whereas furin could not process proBMP6. These results suggest that PACE 4 may regulate the rate of hypertrophic conversion of ATDC 5 cells through activation of proBMP6.