Mechanical and physicochemical regulation of the action of insulin-like growth factor-I on articular cartilage

Lawrence J. Bonassar, Alan J. Grodzinsky, Aneetha Srinivasan, Salomon G. Davila, Stephen B. Trippel

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

The development and maintenance of healthy joints is a complex process involving many physical and biological stimuli. This study investigates the interaction between insulin-like growth factor-I (IGF-I) and static mechanical compression in the regulation of articular cartilage metabolism. Bovine cartilage explants were treated with concentrations of IGF-I from 0 to 300 ng/ml in the presence or absence of 0-50% static compression, and the transient and steady-state incorporation of [3H]proline and [35S]sulfate into matrix components were measured. In parallel studies, cartilage explants were treated with 0-300 ng/ml IGF-I at media pH ranging from 6.4 to 7.2 and the steady-state incorporation of [3H]proline and [35S]sulfate was measured. The effect of 50% static compression on IGF-I transport was determined by measuring the uptake of 125I-labeled IGF-I into cartilage explants. Static compression decreased both [3H]proline and [35S]sulfate incorporation in a dose-dependent manner in the presence or absence of IGF-I. IGF-I increased [3H]proline and [35S]sulfate incorporation in a dose- dependent manner in the presence or absence of compression, but the anabolic effect of the growth factor was lessened when the tissue was compressed by 50%. The response of cartilage explants to IGF-I was similarly lessened in unstrained tissue cultured in media at pH 6.4, a condition which results in a similar intratissue pH to that when cartilage is compressed by 50%. The characteristic time constant (τ) for IGF-I stimulation of cartilage explants was approximately 24 h, while τ for inhibition of biosynthesis by static compression was approximately 2 h. Samples which were both compressed and treated with IGF-I demonstrated an initial decrease in biosynthetic activity at 2 h, followed by an increase at 24 h. Static compression did not alter τ for 125I-labeled IGF-I transport into cartilage but decreased the concentration of 125I-labeled IGF-I in the tissue at equilibrium. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume379
Issue number1
DOIs
StatePublished - Jul 1 2000

Keywords

  • Cartilage biomechanics
  • Chondrocyte metabolism
  • IGF-I
  • Matrix assembly
  • Physical stimuli

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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