Mechanical compression of articular cartilage induces chondrocyte proliferation and inhibits proteoglycan synthesis by activation of the ERK pathway: Implications for tissue engineering and regenerative medicine

James A. Ryan, Eric A. Eisner, Grayson DuRaine, Zongbing You, A Hari Reddi

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Articular cartilage is recalcitrant to endogenous repair and regeneration and is thus a focus of tissue engineering and regenerative medicine strategies. A prerequisite for articular cartilage tissue engineering is an understanding of the signal transduction pathways involved in mechanical compression during trauma or disease. We sought to explore the role of the extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway in chondrocyte proliferation and proteoglycan synthesis following acute mechanical compression. Bovine articular cartilage explants were cultured with and without the ERK 1/2 pathway inhibitor PD98059. Cartilage explants were statically loaded to 40% strain at a strain rate of 1/s for 5 s. Control explants were cultured under similar conditions but were not loaded. There were four experimental groups: (a) no load, without inhibitor; (b) no load, with the inhibitor PD98059; (c) loaded, without the inhibitor; and (d) loaded, with the inhibitor PD98059. The explants were cultured for varying durations from 5 min to 5 days and were then analysed by biochemical and immunohistochemical methods. Mechanical compression induced phosphorylation of ERK 1/2, and this was attenuated with the ERK 1/2 pathway inhibitor PD98059 in a dose-dependent manner. Chondrocyte proliferation was increased by mechanical compression. This effect was blocked by the inhibitor of the ERK 1/2 pathway. Mechanical compression also led to a decrease in proteoglycan synthesis that was reversed with inhibitor PD98059. In conclusion, the ERK 1/2 pathway is involved in the proliferative and biosynthetic response of chondrocytes following acute static mechanical compression.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume3
Issue number2
DOIs
StatePublished - 2009

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Keywords

  • Articular cartilage
  • Chondrocyte proliferation
  • Extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway
  • Mechanical compression
  • Proteoglycan synthesis
  • Regenerative medicine
  • Tissue engineering

ASJC Scopus subject areas

  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Biomaterials

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