Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis

J Orthop Res. 2006 Aug;24(8):1782-90. doi: 10.1002/jor.20211.

Abstract

Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.

MeSH terms

  • Animals
  • Cattle
  • Cell Survival / physiology
  • Cells, Cultured
  • Chondrocytes / cytology*
  • Chondrocytes / drug effects
  • Chondrocytes / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Lipoproteins, LDL / metabolism*
  • Lipoproteins, LDL / pharmacology
  • Osteoarthritis / metabolism
  • Osteoarthritis / physiopathology
  • Proteoglycans / biosynthesis
  • Receptors, Oxidized LDL / genetics
  • Receptors, Oxidized LDL / metabolism*
  • Tensile Strength / physiology*

Substances

  • Lipoproteins, LDL
  • Proteoglycans
  • Receptors, Oxidized LDL
  • oxidized low density lipoprotein