title: Changes in proteoglycans of intervertebral disc in diabetic patients. A possible cause of increased back pain.
abstract: METHODS
  Characterization of the analytic profile of proteoglycans in the intervertebral discs at L4-L5 of nondiabetic (n = 5) and diabetic (n = 5) age-matched subjects. The discs used were discarded material from operations.
  
  
  OBJECTIVE
  To clarify the reason for the higher risk of disc prolapse in diabetic patients.
  
  
  BACKGROUND
  The pathogenesis of diabetes results from a combination of neurologic dysfunctions and a yet undefined metabolic failure, which leads to an abnormal proteoglycan profile.
  
  
  METHODS
  The following methods were used to determine the proteoglycan profile: the measurement of 35S-sulfate uptake per gram wet tissue into sulfated glycosaminoglycan using fresh tissue explants; extraction of proteoglycans by 4 M guanidinium chloride containing protease inhibitors, with further purification by ultracentrifugation on cesium chloride buoyant density gradient under dissociative conditions; total uronic acid and protein contents in the various gradient fractions; assessing the length of sugar side chains of isolated 35Sulfate-glycosaminoglycan molecules by separation of the glycosaminoglycan molecules on a Sepharose 6B-CL column; and paper chromatography of the final digest products of glycosaminoglycan molecules obtained by chondroitinase ABC, a glycosaminoglycan-degrading enzyme.
  
  
  RESULTS
  The findings show that discs from normal nondiabetic subjects have 15 times the rate of 35Sulfate incorporation into glycosaminoglycan molecules than do discs of diabetic patients. The proteoglycans of diabetic patients are banded at a lower buoyant density, indicating a lowered glycosylation rate and a lower number of sugar side chains per core protein. In discs of diabetic patients, there is a slight increase in the chain length of chondroitin sulfate. Further analysis of the glycosaminoglycan chains showed a decreased amount of keratan sulfate, compared with that in nondiabetic subjects. However, the total uronic acid content of the disc tissues and the ratio of uronic acid to protein of each fraction were unchanged in diabetic patients versus that in control subjects.
  
  
  CONCLUSIONS
  Discs in patients with diabetes have proteoglycans with lower buoyant density and substantially undersulfated glycosaminoglycan, which with the specific neurologic damage in these patients, might lead to increased susceptibility to disc prolapse.
authors.affiliation: Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Robinson
authors.forename: Y
authors.initials: Y
authors.lastname: Mirovsky
authors.forename: N
authors.initials: N
authors.lastname: Halperin
authors.forename: Z
authors.initials: Z
authors.lastname: Evron
authors.forename: Z
authors.initials: Z
authors.lastname: Nevo
mesh_terms: D000368:Aged; D002809:Chondroitin Sulfates / Q000737:chemistry; D002849:Chromatography, Gas; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000601:surgery; D007405:Intervertebral Disc Displacement / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007632:Keratan Sulfate / Q000032:analysis; D017116:Low Back Pain / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism*; D014574:Uronic Acids / Q000032:analysis
chemical_list: D006025:Glycosaminoglycans; D011509:Proteoglycans; D014574:Uronic Acids; D002809:Chondroitin Sulfates; D007632:Keratan Sulfate