Transforming growth factor-beta 1 stimulates synthesis of proteoglycan aggregates in calf articular cartilage organ cultures

Arch Biochem Biophys. 1991 Apr;286(1):99-106. doi: 10.1016/0003-9861(91)90013-9.


Previous work showed that transforming growth factor-beta 1 (TGF-beta 1), added alone to bovine cartilage organ cultures, stimulated [35S]sulfate incorporation into macromolecular material but did not investigate the fidelity of the stimulated system to maintain synthesis of cartilage-type proteoglycans. This paper provides evidence that chondrocytes synthesize the appropriate proteoglycan matrix under TGF-beta 1 stimulation: (i) there is a coordinated increase in hyaluronic acid and proteoglycan monomer synthesis, (ii) link-stable proteoglycan aggregates are assembled, (ii) the hybrid chondroitin sulfate/keratan sulfate monomeric species is synthesized, and (iv) there is an increase in protein core synthesis. Some variation in glycosylation patterns was observed when proteoglycans synthesized under TGF-beta 1 stimulation were compared to those synthesized under basal conditions. Thus comparing TGF-beta 1 to basal samples respectively, the monomers were larger (Kav on Sepharose CL-2B = 0.29 vs 0.41), the chondroitin sulfate chains were longer by approximately 3.5 kDa, the percentage of total glycosaminoglycan in keratan sulfate increased slightly from approximately 4% (basal) to approximately 6%, and the unsulfated disaccharide decreased from 28% (basal) to 12%. All of these variations are in the direction of a more anionic proteoglycan. Since the ability of proteoglycans to confer resiliency to the cartilage matrix is directly related to their anionic nature, these changes would presumably have a beneficial effect on tissue function.

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Cattle
  • Chondroitin Sulfates / isolation & purification
  • Disaccharides / analysis
  • Glycosaminoglycans / biosynthesis
  • Glycosaminoglycans / isolation & purification
  • Hyaluronic Acid / isolation & purification
  • Macromolecular Substances
  • Organ Culture Techniques
  • Proteoglycans / biosynthesis*
  • Proteoglycans / isolation & purification
  • Sulfates / metabolism
  • Sulfur Radioisotopes
  • Transforming Growth Factor beta / pharmacology*


  • Disaccharides
  • Glycosaminoglycans
  • Macromolecular Substances
  • Proteoglycans
  • Sulfates
  • Sulfur Radioisotopes
  • Transforming Growth Factor beta
  • Hyaluronic Acid
  • Chondroitin Sulfates