The sulfation pattern of chondroitin sulfate from articular cartilage explants in response to mechanical loading

Biochim Biophys Acta. 2003 Jul 30;1638(3):241-8. doi: 10.1016/s0925-4439(03)00089-9.


Chondrocytes within articular cartilage experience complete unloading between loading cycles thereby utilizing mechanical signals to regulate their own anabolic and catabolic activities. Structural alterations of proteoglycans (PGs) during aging and the development of osteoarthritis (OA) have been reported; whether these can be attributed to altered load or compression is largely unknown. We report here on experiments in which the effect of intermittent loading on the fine structure of newly synthesized chondroitin sulfate (CS) in bovine articular cartilage explants was examined. Tissues were subjected for 6 days to cyclic compressive pressure using a sinusoidal waveform of 0.1, 0.5 or 1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5, 10 or 20 s, followed by an unloading period lasting 10, 100 or 1000 s. During the final 18 h of the culture, cartilage explants were radiolabeled with 50 microCi/ml D-6-[3H]glucosamine, and newly synthesized as well as endogenous CS chains were isolated after proteinase solubilization of the tissue. CS chains were depolymerized with chondroitinase ABC and ACII, and the 3H-digestion products were quantified after fractionation by high-performance anion-exchange chromatography using a CarboPac PA1 column. Intermittently applied cyclic mechanical loading did not affect the proportion of 4- and 6-sulfated disaccharide repeats, but caused a significant decrease in the abundance of the 4,6-disulfated nonreducing terminal galNAc residues. In addition, loading induced elongation of CS chains. Taken together, these data provide evidence for the first time that long-term in vitro loading results in marked and reproducible changes in the fine structure of newly synthesized CS, and that accumulation of such chains may in turn modify the physicochemical and biological response of articular cartilage. Moreover, data presented here suggest that in vitro dynamic compression of cartilage tissue can induce some of the same alterations in CS sulfation that have previously been shown to occur during the development of degenerative joint diseases such as OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomechanical Phenomena
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / physiology*
  • Chondroitin Sulfates / chemistry
  • Chondroitin Sulfates / metabolism*
  • Disaccharides / chemistry
  • Disaccharides / metabolism
  • Humans
  • In Vitro Techniques
  • Osteoarthritis / physiopathology
  • Oxidation-Reduction
  • Sulfotransferases
  • Sulfur / chemistry
  • Sulfur / metabolism*
  • Time Factors
  • Weight-Bearing / physiology


  • Disaccharides
  • Sulfur
  • Chondroitin Sulfates
  • N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase
  • Sulfotransferases