Mechanisms involved in inhibition of chondrogenesis by activin-A

Sho Mitsugi, Wataru Ariyoshi, Toshinori Okinaga, Takeshi Kaneuji, Yoshihiro Kataoka, Tetsu Takahashi, Tatsuji Nishihara

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: Activin-A, a member of the TGF-β family, is known to be present in bone and cartilage. Although, involvement of the TGF-β 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.

Original languageEnglish
Pages (from-to)380-384
Number of pages5
JournalBiochemical and biophysical research communications
Volume420
Issue number2
DOIs
Publication statusPublished - 2012 Apr 6
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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