Mechanisms involved in inhibition of chondrogenesis by activin-A

作者：Mitsugi Sho; Ariyoshi Wataru; Okinaga Toshinori; Kaneuji Takeshi; Kataoka Yoshihiro; Takahashi Tetsu; Nishihara Tatsuji^*

来源：Biochemical and Biophysical Research Communications, 2012, 420(2): 380-384.

DOI：10.1016/j.bbrc.2012.03.003

• Activin-A
• Chondrocyte
• Smad
• JNK
• Akt

Objectives: Activin-A, a member of the TGF-beta family, is known to be present in bone and cartilage. Although, involvement of the TGF-beta family in chondrogenesis has been reported, the mechanism by which activin-A regulates chondrogenesis has not been fully elucidated. The aim of this study was to investigate the effects of activin-A on chondrocyte differentiation in vitro.
Materials and methods: Monolayer cultures of mouse chondrocyte ATDC cells were pretreated with a variety of inhibitors of major signaling pathways prior to addition of activin-A. The expressions of sox9, runx2, and osterix mRNA were detected using real-time PCR. To determine chondrocyte differentiation, sulfated glycosaminoglycans were stained with Alcian blue. To further elucidate the role of activin-A on chondrogenesis regulation, phosphorylation of Smad2/3, ERK, JNK, and Akt proteins was determined by western blotting.
Results: Activin-A suppressed the transcription of sox9, runx2, and osterix mRNA, as well as sulfated glycosaminoglycans accumulation. Activin-A also inhibited constitutive phosphorylation of JNK and Akt proteins. Furthermore, inhibition of the JNK and PI3K-Akt pathways by chemical inhibitors suppressed chondrogenesis in ATDC5 cells.
Conclusions: These results indicate that activin-A may suppress chondrocyte differentiation in ATDC5 cells via down-regulation of JNK and Akt phosphorylation.

• 出版日期2012-4-6