Regulation of chondrocytic gene expression by biomechanical signals

Crit Rev Eukaryot Gene Expr. 2008;18(2):139-50. doi: 10.1615/critreveukargeneexpr.v18.i2.30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Cartilage / physiology
  • Chondrocytes / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Inflammation / etiology
  • Inflammation / genetics
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Mechanotransduction, Cellular / genetics*
  • Models, Biological
  • NF-kappa B / physiology
  • Regeneration / physiology
  • Transcription, Genetic
  • Wounds and Injuries / physiopathology


  • Inflammation Mediators
  • NF-kappa B