Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction

H-S Lee, S J Millward-Sadler, M O Wright, G Nuki, R Al-Jamal, D M Salter

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: The objective of this study was to examine PKC isozyme expression in human articular chondrocytes and assess roles for RACK1, a receptor for activated C kinase in the mechanotransduction process.

METHODS: Primary cultures of human articular chondrocytes and a human chondrocyte cell line were studied for expression of PKC isozymes and RACK1 by western blotting. Following mechanical stimulation of chondrocytes in vitro in the absence or presence of anti-integrin antibodies and RGD containing oligopeptides, subcellular localization of PKCalpha and association of RACK1 with PKCalpha and beta1 integrin was assessed.

RESULTS: Human articular chondrocytes express PKC isozymes alpha, gamma, delta, iota, and lambda. Following mechanical stimulation at 0.33Hz chondrocytes show a rapid, beta1 integrin dependent, translocation of PKCalpha to the cell membrane and increased association of RACK1 with PKCalpha and beta1 integrin.

CONCLUSIONS: RACK1 mediated translocation of activated PKCalpha to the cell membrane and modulation of integrin-associated signaling are likely to be important in regulation of downstream signaling cascades controlling chondrocyte responses to mechanical stimuli.

Original languageEnglish
Pages (from-to)890-7
Number of pages8
JournalOsteoarthritis and Cartilage
Volume10
Issue number11
Publication statusPublished - Nov 2002

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Cartilage, Articular
  • Cell Line
  • Chondrocytes
  • Female
  • Humans
  • Integrin beta Chains
  • Isoenzymes
  • Male
  • Mechanotransduction, Cellular
  • Middle Aged
  • Peptides
  • Pressure
  • Protein Kinase C
  • Receptors, Cell Surface

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