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

Osteoarthritis Cartilage. 2002 Nov;10(11):890-7. doi: 10.1053/joca.2002.0842.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Integrin beta Chains
  • Isoenzymes
  • Peptides
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • peptide I
  • Protein Kinase C