Transforming growth factor-beta 1 stimulates synthesis of proteoglycan aggregates in calf articular cartilage organ cultures.
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.
Morales
T I
TI
Bone Research Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002809:Chondroitin Sulfates / Q000302:isolation & purification; D004187:Disaccharides / Q000032:analysis; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000302:isolation & purification; D006820:Hyaluronic Acid / Q000302:isolation & purification; D046911:Macromolecular Substances; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000096:biosynthesis* / Q000302:isolation & purification; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D004187:Disaccharides; D006025:Glycosaminoglycans; D046911:Macromolecular Substances; D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates