The degradation of cartilage proteoglycans by tissue proteinases. Proteoglycan heterogeneity and the pathway of proteolytic degradation.
1. CaCl2-extracted proteoglycan from bovine nasal cartilage was degraded by four tissue proteinases till no further decrease in hydroynamic size was obtained. The proteoglycan and its final degradation products were then fractionated by Sepharose 2B chromatography. 2. The average size of the degradation products was least for cathepsin B and lysosomal elastase, and greatest for cathepsin D and cathepsin G. The latter two proteinases also produced degradation products that showed the widest range of sizes. 3. The structure of the degradation products ranged from peptides containing a single glycosaminoglycan chain to those containing twelve or more chains. Of the four proteinases, only cathepsin B produced peptides that contained a single chondroitin sulphate chain. 4.  The proteoglycan was very heterogeneous with respect to size and chemical composition. Its behaviour on electrophoresis suggested that at least two genetically distinct core proteins might exist. 5. Irrespective of their structural variations, all proteoglycan molecules were able to interact with hyaluronic acid. In contrast, none of the degradation products were capable of this type of interaction. 6. A pathway for the proteolytic degradation of proteoglycans is postulated in which the sites of initial cleavage may be common to the majority of proteinases, whereas the production of the final clusters is dependent on the specificity of the proteinase. Only those proteinases of broadest specificity can produce single-chain chondroitin sulphate-peptides.
D000818:Animals; D002122:Calcium Chloride; D002356:Cartilage / Q000032:analysis*; D002403:Cathepsins; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002847:Chromatography, Agarose; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D008956:Models, Chemical; D010196:Pancreatic Elastase; D011509:Proteoglycans / Q000032:analysis*
D011509:Proteoglycans; D002403:Cathepsins; D010450:Endopeptidases; D010196:Pancreatic Elastase; D002122:Calcium Chloride