Regulation of chondrocytic gene expression by biomechanical signals.

Journal Article (Journal Article;Review)

Cartilage is a mechanosensitive tissue, which means that it can perceive and respond to biomechanical signals. Despite the known importance of biomechanical signals in the etiopathogenesis of arthritic diseases and their effectiveness in joint restoration, little is understood about their actions at the cellular level. Recent molecular approaches have revealed that specific biomechanical stimuli and cell interactions generate intracellular signals that are powerful inducers or suppressors of proinflammatory and reparative genes in chondrocytes. Biomechanical signals are perceived by cartilage in magnitude-, frequency-, and time-dependent manners. Static and dynamic biomechanical forces of high magnitudes induce proinflammatory genes and inhibit matrix synthesis. Contrarily, dynamic biomechanical signals of low/physiologic magnitudes are potent antiinflammatory signals that inhibit interleukin-1beta (IL-1beta)-induced proinflammatory gene transcription and abrogate IL-1beta/tumor necrosis factor-alpha-induced inhibition of matrix synthesis. Recent studies have identified nuclear factor-kB (NF-kB) transcription factors as key regulators of biomechanical signal-mediated proinflammatory and antiinflammatory actions. These signals intercept multiple steps in the NF-kappaB signaling cascade to regulate cytokine gene expression. Taken together, these findings provide insight into how biomechanical signals regulate inflammatory and reparative gene transcription, underscoring their potential in enhancing the ability of chondrocytes to curb inflammation in diseased joints.

Full Text

Duke Authors

Cited Authors

  • Knobloch, TJ; Madhavan, S; Nam, J; Agarwal, S; Agarwal, S

Published Date

  • 2008

Published In

Volume / Issue

  • 18 / 2

Start / End Page

  • 139 - 150

PubMed ID

  • 18304028

Pubmed Central ID

  • PMC4967411

International Standard Serial Number (ISSN)

  • 1045-4403

Digital Object Identifier (DOI)

  • 10.1615/critreveukargeneexpr.v18.i2.30


  • eng

Conference Location

  • United States