Electron microscopic studies of cartilage proteoglycans.
Proteoglycans, molecules consisting of glycosaminoglycan chains bound to protein, form a significant part of the cartilage extracellular matrix. Biochemical and biophysical methods describe the average composition and physical properties of these polydispense molecules. Electron microscopy reveals the structure and dimensions of individual proteoglycans. Examination of individual molecules can confirm or challenge concepts of their structure developed from studies of their chemical composition and physical properties, and may suggest new directions for biochemical investigation. Electron microscopy has confirmed that cartilage proteoglycans exist on two levels of organization: monomers consisting of central protein core filaments with attached glycosaminoglycan chains and aggregates consisting of central hyaluronate filaments with multiple attached monomers. Most aggregated monomers have a thin segment which attaches to the hyaluronate filament and probably represents primarily the keratan sulfate rich region of the protein core, and a peripheral thick segment that represents the chondroitin sulfate rich region and in some monomers part of the keratan sulfate rich region. Proteoglycans vary considerably in size, charge and composition. Direct visualization of proteoglycan aggregates and nonaggregated monomers has helped explain the structural basis of this polydispensity. Monomers vary in protein core length, number of glycosaminoglycan chains and length of the glycosaminoglycan chains. Aggregates vary in hyaluronate filament length, spacing between monomers, number of monomers per aggregate, and aggregated monomer length. In most populations of aggregates, from most tissues, variability in the number of monomers per aggregate produces most of the difference in aggregate size. Link proteins, small proteins that bind to monomers and hyaluronate, help determine aggregate size and the proportion of monomers that aggregate. Experiments in vitro show that link protein can increase aggregate size four fold, make the spacing between aggregated monomers more regular and increase the proportion of monomers that aggregate ten fold. With increasing age, cartilage proteoglycan monomers become shorter, more variable in length, have shorter chondroitin sulfate chain clusters and have a shorter thin segment which may result from an increase in keratan sulfate content. Study of monomers newly synthesized by calf and steer chondrocytes suggests that the age related changes in monomer structure result largely from changes in proteoglycan synthesis or intracellular processing. Aggregates also change with age. They become shorter, have fewer monomers per aggregate and have shorter aggregated monomers. In addition, the proportion of monomers that aggregate decreases. These age related changes in proteoglycan aggregation may result from a decreasing concentration of functional link protein or from accumulation of fragments of the protein core containing the hyaluronic acid binding region.(ABSTRACT TRUNCATED AT 400 WORDS)
Buckwalter
J A
JA
Veterans Administration Medical Center, Iowa City, IA.
Rosenberg
L C
LC
D000375:Aging / Q000378:metabolism; D000818:Animals; D002240:Carbohydrate Sequence; D002356:Cartilage / Q000737:chemistry / Q000648:ultrastructure*; D002358:Cartilage, Articular / Q000737:chemistry / Q000648:ultrastructure; D002813:Chondrosarcoma / Q000737:chemistry / Q000648:ultrastructure; D006132:Growth Plate / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D007403:Intervertebral Disc / Q000737:chemistry / Q000648:ultrastructure; D008592:Menisci, Tibial / Q000737:chemistry / Q000648:ultrastructure; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000648:ultrastructure; D011509:Proteoglycans / Q000302:isolation & purification / Q000648:ultrastructure*
D009363:Neoplasm Proteins; D011509:Proteoglycans