Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes

Takeshi Yanagita, Satoshi Kubota, Harumi Kawaki, Kazumi Kawata, Seiji Kondo, Teruko Takano-Yamamoto, Shinji Tanaka, Masaharu Takigawa

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

CCN4/Wnt-induced secreted protein 1 (WISP1) is one of the CCN (CTGF/Cyr61/Nov) family proteins. CCN members have typical structures composed of four conserved cysteine-rich modules and their variants lacking certain modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. Several previous reports described a CCN4/WISP1 variant (WISP1v) lacking the second module in a few malignancies, but no information concerning the production of WISP1 variants in normal tissue is currently available. The expression of CCN4/WISP1 mRNA and its variants were analyzed in a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8, and primary rabbit growth cartilage (RGC) chondrocytes. First, we found WISP1v and a novel variant of WISP1 (WISP1vx) to be expressed in HCS-2/8, as well as full-length WISP1 mRNA. This new variant was lacking the coding regions for the second and third modules and a small part of the first module. To monitor the expression of CCN4/WISP1 mRNA along chondrocyte differentiation, RGC cells were cultured and sampled until they were mineralized. As a result, we identified a WISP1v ortholog in normal RGC cells. Interestingly, the WISP1v mRNA level increased dramatically along with terminal differentiation. Furthermore, overexpression of WISP1v provoked expression of an alkaline phosphatase gene that is a marker of terminal differentiation in HCS-2/8 cells. These findings indicate that WISP1v thus plays a critical role in chondrocyte differentiation toward endochondral ossification, whereas HCS-2/8-specific WISP1vx may be associated with the transformed phenotypes of chondrosarcomas.

Original languageEnglish
Pages (from-to)1655-1665
Number of pages11
JournalFEBS Journal
Volume274
Issue number7
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Chondrocytes
Messenger RNA
Cartilage
Proteins
Chondrosarcoma
Rabbits
Growth
Genes
Differentiation Antigens
Alternative Splicing
Osteogenesis
Cysteine
Alkaline Phosphatase
Cultured Cells
Cells
Tissue
Phenotype
Cell Line
Mutation
Neoplasms

Keywords

  • Cartilage
  • CCN family
  • Chondrocyte differentiation
  • Splicing variant
  • Wnt-induced secreted protein 1 (WISP1)

ASJC Scopus subject areas

  • Biochemistry

Cite this

Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes. / Yanagita, Takeshi; Kubota, Satoshi; Kawaki, Harumi; Kawata, Kazumi; Kondo, Seiji; Takano-Yamamoto, Teruko; Tanaka, Shinji; Takigawa, Masaharu.

In: FEBS Journal, Vol. 274, No. 7, 04.2007, p. 1655-1665.

Research output: Contribution to journalArticle

Yanagita, Takeshi ; Kubota, Satoshi ; Kawaki, Harumi ; Kawata, Kazumi ; Kondo, Seiji ; Takano-Yamamoto, Teruko ; Tanaka, Shinji ; Takigawa, Masaharu. / Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes. In: FEBS Journal. 2007 ; Vol. 274, No. 7. pp. 1655-1665.
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