Molecular mechanism of basic calcium phosphate crystal-induced mitogenesis. Role of protein kinase C

P. G. Mitchell, W. J. Pledger, Herman S Cheung

Research output: Contribution to journalArticle

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Abstract

Synovial tissue hyperplasia in basic calcium phosphate deposition diseases has been suggested to develop through the stimulation of cell growth by basic calcium phosphate (BCP) crystals deposited in joints. These crystals have been used in vitro to stimulate DNA synthesis in quiescent fibroblasts to experimentally study this proliferative disease. The stimulation of DNA synthesis, in density-arrested Balb/c 3T3 cells, by BCP crystals was inhibited after down-regulating protein kinase C activity with 12-O-tetradecanoylphorbol 13-acetate (TPA). No effect on platelet-derived growth factor (PDGF)-stimulated DNA synthesis was observed under the same conditions. The expression of c-myc and c-fos increased in response to BCP stimulation in a manner similar to the increase produced by stimulation with PDGF. The BCP stimulation of c-fos and c-myc messages was inhibited 60 and 90%, respectively, in TPA-pretreated, protein kinase C-down-regulated cells. The induction of these transcripts by PDGF was unaffected in cells pretreated with TPA. TPA was unable to stimulate c-fos and c-myc expression or DNA synthesis following protein kinase C down-regulation. Both PDGF and TPA stimulated phosphorylation of an 80-kDa protein, whereas BCP crystals had no effect on phosphorylation of this protein. The exposure of density-arrested Balb/c 3T3 cells to BCP crystals had no effect on high affinity epidermal growth factor receptor binding under conditions in which PDGF and TPA reduced epidermal growth factor binding. The data suggest that PDGF can act to stimulate c-fos and c-myc expression as well as DNA synthesis through a protein kinase C-independent pathway, whereas BCP crystals require at least endogenous levels of protein kinase C to stimulate these events.

Original languageEnglish
Pages (from-to)14071-14077
Number of pages7
JournalJournal of Biological Chemistry
Volume264
Issue number24
StatePublished - Jan 1 1989
Externally publishedYes

Fingerprint

Protein Kinase C
Platelet-Derived Growth Factor
Tetradecanoylphorbol Acetate
Crystals
Acetates
DNA
3T3 Cells
Phosphorylation
calcium phosphate
Cell growth
Fibroblasts
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Hyperplasia
Proteins
Down-Regulation
Joints
Tissue
Growth

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular mechanism of basic calcium phosphate crystal-induced mitogenesis. Role of protein kinase C. / Mitchell, P. G.; Pledger, W. J.; Cheung, Herman S.

In: Journal of Biological Chemistry, Vol. 264, No. 24, 01.01.1989, p. 14071-14077.

Research output: Contribution to journalArticle

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