Reference - Detail
RRC ID | 43732 |
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Author | Mitsugi S, Ariyoshi W, Okinaga T, Kaneuji T, Kataoka Y, Takahashi T, Nishihara T. |
Title | Mechanisms involved in inhibition of chondrogenesis by activin-A. |
Journal | Biochem Biophys Res Commun |
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. |
Volume | 420(2) |
Pages | 380-4 |
Published | 2012-4-6 |
DOI | 10.1016/j.bbrc.2012.03.003 |
PII | S0006-291X(12)00441-X |
PMID | 22425773 |
MeSH | Activins / pharmacology Activins / physiology* Animals Cell Differentiation* / drug effects Cells, Cultured Chondrocytes / cytology* Chondrocytes / drug effects Chondrocytes / metabolism Chondrogenesis* / drug effects Core Binding Factor Alpha 1 Subunit / biosynthesis Mice Receptors, Transforming Growth Factor beta / antagonists & inhibitors SOX9 Transcription Factor / biosynthesis Sp7 Transcription Factor Transcription Factors / biosynthesis |
IF | 2.985 |
Times Cited | 9 |
WOS Category | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
Resource | |
Human and Animal Cells | ATDC5(RCB0565) |