Restoration by parathyroid hormone and dibutyryl cyclic AMP of expression of the differentiated phenotype of chondrocytes inhibited by a tumor promoter, 12-0-tetradecanoylphorbol-13-acetate

Masaharu Takigawa, Keisuke Fukuo, Teruko Takano, Fujio Suzuki

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

12-0-Tetradecanoylphorbol-13-acetate (TPA) inhibited expression of the differentiated phenotype of chondrocytes in rabbit costal chondrocytes in culture. TPA transformed typical polygonal chondrocytes into multilayered, fibroblastic cells and also inhibited the rate of [35S]sulfate incorporation into glycosaminoglycan (GAG), a differentiated phenotype of chondrocytes. These changes were apparent within 24 h and reached a plateau at 48 h after the addition of TPA. Phorbol didecanoate and phorbol dibenzoate also inhibited sulfation of GAG, even though the effect was weaker than that of TPA. Phorbol diacetate and 4-0-methyl TPA did not inhibit sulfation of GAG. Addition of parathyroid hormone (PTH) or dibutyryl cyclic AMP simultaneously with TPA overcame the inhibition caused by TPA. PTH and dibutyryl cyclic AMP also reversed the inhibition and stimulated expression of the differentiated phenotype of chondrocytes even in de-differentiated cells which had been pretreated for 3 days with TPA. These findings suggest that cyclic AMP plays an important role in the restoration of the differentiated phenotype of chondrocytes in TPA-treated chondrocytes, and that the TPA-treated cells retain some of the differentiated phenotype of the original cells, such as responsiveness to PTH.

Original languageEnglish
Pages (from-to)283-291
Number of pages9
JournalCell Differentiation
Volume13
Issue number4
DOIs
Publication statusPublished - Dec 1983
Externally publishedYes

Keywords

  • 12-0-tetradecanoylphorbol-13-acetate
  • cultured chondrocytes
  • cyclic AMP
  • differentiation
  • glycosaminoglycan biosynthesis
  • parathyroid hormone

ASJC Scopus subject areas

  • Developmental Biology

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